<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>2341-4545</journal-id>
<journal-title><![CDATA[GE-Portuguese Journal of Gastroenterology]]></journal-title>
<abbrev-journal-title><![CDATA[GE Port J Gastroenterol]]></abbrev-journal-title>
<issn>2341-4545</issn>
<publisher>
<publisher-name><![CDATA[Sociedade Portuguesa de Gastrenterologia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S2341-45452022000100013</article-id>
<article-id pub-id-type="doi">10.1159/000516009</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Phenotype-Genotype Correlation in Colorectal Cancer: A Real-Life Study]]></article-title>
<article-title xml:lang="pt"><![CDATA[Correlação fenótipo-genótipo no cancro colo-rectal: estudo da vida real]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Frias-Gomes]]></surname>
<given-names><![CDATA[Catarina]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sousa]]></surname>
<given-names><![CDATA[Ana Carla]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rolim]]></surname>
<given-names><![CDATA[Inês]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Henriques]]></surname>
<given-names><![CDATA[Ana Raquel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Branco]]></surname>
<given-names><![CDATA[Francisco]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Janeiro]]></surname>
<given-names><![CDATA[André]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Malveiro]]></surname>
<given-names><![CDATA[Sara]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Dário]]></surname>
<given-names><![CDATA[Ana Rita]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Oliveira]]></surname>
<given-names><![CDATA[Maria Helena]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Borralho]]></surname>
<given-names><![CDATA[Paula]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Teixeira]]></surname>
<given-names><![CDATA[José Alberto]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Faria]]></surname>
<given-names><![CDATA[Ana]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Maio]]></surname>
<given-names><![CDATA[Rui]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Fonseca]]></surname>
<given-names><![CDATA[Isabel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cravo]]></surname>
<given-names><![CDATA[Marília]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Hospital Beatriz Ângelo Departamento de Cirurgia Serviço de Gastrenterologia]]></institution>
<addr-line><![CDATA[Loures ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Instituto de Medicina Molecular Genomed ]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Instituto Português de Oncologia Francisco Gentil Serviço de Anatomia Patológica ]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidade de Lisboa Faculdade de Medicina Instituto de Anatomia Patológica]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af5">
<institution><![CDATA[,Hospital Beatriz Ângelo Departamento de Oncologia Serviço de Oncologia Médica]]></institution>
<addr-line><![CDATA[Loures ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af6">
<institution><![CDATA[,Hospital Beatriz Ângelo Serviço de Anatomia Patológica ]]></institution>
<addr-line><![CDATA[Loures ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af7">
<institution><![CDATA[,Hospital CUF Descobertas Serviço de Anatomia Patológica ]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af8">
<institution><![CDATA[,Hospital Beatriz Ângelo Departamento de Cirurgia Serviço de Cirurgia Geral]]></institution>
<addr-line><![CDATA[Loures ]]></addr-line>
<country>Portugal</country>
</aff>
<pub-date pub-type="pub">
<day>28</day>
<month>02</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="epub">
<day>28</day>
<month>02</month>
<year>2022</year>
</pub-date>
<volume>29</volume>
<numero>1</numero>
<fpage>13</fpage>
<lpage>21</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_arttext&amp;pid=S2341-45452022000100013&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_abstract&amp;pid=S2341-45452022000100013&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_pdf&amp;pid=S2341-45452022000100013&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract  Background and Aims:  Colorectal cancer (CRC) is a heterogeneous disease with distinctive genetic pathways, such as chromosomal instability, microsatellite instability and methylator pathway. Our aim was to correlate clinical and genetic characteristics of CRC patients in order to understand clinical implications of tumour genotype.  Methods:  Single-institution retrospective cohort of patients who underwent curative surgery for CRC, from 2012 to 2014. RAS and BRAF mutations were evaluated with the real-time PCR technique Idylla®. Mismatch repair deficiency (dMMR) was characterized by absence of MLH1, MSH6, MSH2 and/or PMS2 expression, evaluated by tissue microarrays. Overall survival (OS) and disease-free survival (DFS) were assessed using survival analysis.  Results:  Overall, 242 patients were included (males 57.4%, age 69.3 ± 12.9 years; median follow-up 49 months). RAS-mutated tumours were associated with reduced DFS (p = 0.02) and OS (p = 0.045) in stage I-III CRC. BRAF-mutated tumours were more predominant in females and in the right colon, similarly to dMMR tumours. BRAF status did not influence OS (4 years)/DFS (3.5 years) in stage I-III disease. However, after relapse, length of survival was 3.5 months in BRAF-mutated tumours in contrast to 18.6 months in BRAF wild-type tumours (p = NS). No germline mutations in mismatch repair genes were so far identified in the patients with dMMR tumours. Molecular phenotype (RAS, BRAF and MMR) did not influence OS in metastatic patients. Our small sample size may be a limitation of the study.  Conclusion:  In our cohort, RAS-mutated tumours were associated with worse DFS and OS in early-stage CRC, whereas the remaining molecular variables had no prognostic influence.]]></p></abstract>
<abstract abstract-type="short" xml:lang="pt"><p><![CDATA[Resumo  Introdução:  O cancro colo-rectal (CCR) é uma doença heterogénea, com vias genéticas distintas, nomeadamente instabilidade cromossómica, instabilidade de microssatélites e via metiladora. O nosso objetivo foi correlacionar as características clínicas e genéticas dos doentes com CCR e, deste modo, conhecer as implicações na prática clínica do genótipo tumoral.  Métodos:  Estudo de coorte retrospectivo unicêntrico de doentes diagnosticados com CCR e submetidos a cirurgia com intuito curativo, entre 2012 e 2014. As mutações RAS e BRAF foram avaliadas pela técnica de real time PCR Idylla®. A deficiência de mismatch repair(MMR) foi avaliada pela técnica de tissue microarrayse definida pela ausência de expressão de MLH1, MSH6, MSH2 e/ou PMS2. A sobrevivência global (SG) e a sobrevivência livre de doença (SLD) foram avaliadas por análise de sobrevivência.  Resultados:  No total, foram incluídos 242 doentes (homens 57.4%, idade 69.3 ± 12.9 anos, mediana de seguimento de 49 meses). Os tumores RAS-mutados associaram-se a menor SLD (p = 0.02) e SG (p = 0.045) em doentes com CCR estadio I-III. Os tumores BRAF-mutados foram mais frequentes em mulheres e nos tumores do cólon direito, assim como os tumores com deficiência para MMR. O status BRAF não influenciou a SG (4 anos)/SLD (3.5 anos) nos estadio I-III. Contudo, após a recidiva, o tempo de sobrevivência foi de 3.5 meses nos tumores BRAF-mutados, em comparação com 18.6 meses nos tumores sem esta mutação (p = NS). Não se identificaram mutações germinativas nos genes de mismatch repair nos doentes com tumores deficientes para estas proteinas (dMMR). O perfil molecular (RAS, BRAF e MMR)não influenciou a sobrevivência global dos doentes com metástases ao diagnóstico. O tamanho da amostra pode ser uma limitação do estudo.  Conclusão:  Na nossa coorte, os tumores RAS-mutados associaram-se a pior SLD e SG nos estádios precoces de CCR. Os restantes marcadores moleculares não influenciaram o prognóstico dos doentes.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Overall survival]]></kwd>
<kwd lng="en"><![CDATA[Disease-free survival]]></kwd>
<kwd lng="en"><![CDATA[RAS]]></kwd>
<kwd lng="en"><![CDATA[BRAF]]></kwd>
<kwd lng="en"><![CDATA[Mismatch repair]]></kwd>
<kwd lng="en"><![CDATA[Tumour heterogeneity]]></kwd>
<kwd lng="pt"><![CDATA[Sobrevivência global]]></kwd>
<kwd lng="pt"><![CDATA[Sobrevivência livre de doença]]></kwd>
<kwd lng="pt"><![CDATA[RAS]]></kwd>
<kwd lng="pt"><![CDATA[BRAF]]></kwd>
<kwd lng="pt"><![CDATA[Mismatch repair]]></kwd>
<kwd lng="pt"><![CDATA[Heterogeneidade tumoral]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<label>1</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Stintzing]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Tejpar]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Gibbs]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Thiebach]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Lenz]]></surname>
<given-names><![CDATA[HJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Understanding the role of primary tumour localisation in colorectal cancer treatment and outcomes]]></article-title>
<source><![CDATA[Eur J Cancer]]></source>
<year>2017</year>
<volume>84</volume>
<page-range>69-80</page-range></nlm-citation>
</ref>
<ref id="B2">
<label>2</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Siegel]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Naishadham]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Jemal]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Cancer statistics, 2013]]></article-title>
<source><![CDATA[CA Cancer J Clin]]></source>
<year>2013</year>
<volume>63</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>11-30</page-range></nlm-citation>
</ref>
<ref id="B3">
<label>3</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Sinicrope]]></surname>
<given-names><![CDATA[FA]]></given-names>
</name>
<name>
<surname><![CDATA[Okamoto]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Kasi]]></surname>
<given-names><![CDATA[PM]]></given-names>
</name>
<name>
<surname><![CDATA[Kawakami]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Molecular Biomarkers in the Personalized Treatment of Colorectal Cancer]]></article-title>
<source><![CDATA[Clin Gastroenterol Hepatol]]></source>
<year>2016</year>
<volume>14</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>651-8</page-range></nlm-citation>
</ref>
<ref id="B4">
<label>4</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Andreyev]]></surname>
<given-names><![CDATA[HJ]]></given-names>
</name>
<name>
<surname><![CDATA[Norman]]></surname>
<given-names><![CDATA[AR]]></given-names>
</name>
<name>
<surname><![CDATA[Cunningham]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Oates]]></surname>
<given-names><![CDATA[JR]]></given-names>
</name>
<name>
<surname><![CDATA[Clarke]]></surname>
<given-names><![CDATA[PA]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Kirsten ras mutations in patients with colorectal cancer the multicenter &amp;raquo;,» &amp;reg;,® &amp;sect;,§ &amp;shy;,­ &amp;sup1;,¹ &amp;sup2;,² &amp;sup3;,³ &amp;szlig;,ß &amp;THORN;,Þ &amp;thorn;,þ &amp;times;,× &amp;Uacute;,Ú &amp;uacute;,ú &amp;Ucirc;,Û &amp;ucirc;,û &amp;Ugrave;,Ù &amp;ugrave;,ù &amp;uml;,¨ &amp;Uuml;,Ü &amp;uuml;,ü &amp;Yacute;,Ý &amp;yacute;,ý &amp;yen;,¥ &amp;yuml;,ÿ &amp;para;,¶ RASCAL &amp;raquo;,» &amp;reg;,® &amp;sect;,§ &amp;shy;,­ &amp;sup1;,¹ &amp;sup2;,² &amp;sup3;,³ &amp;szlig;,ß &amp;THORN;,Þ &amp;thorn;,þ &amp;times;,× &amp;Uacute;,Ú &amp;uacute;,ú &amp;Ucirc;,Û &amp;ucirc;,û &amp;Ugrave;,Ù &amp;ugrave;,ù &amp;uml;,¨ &amp;Uuml;,Ü &amp;uuml;,ü &amp;Yacute;,Ý &amp;yacute;,ý &amp;yen;,¥ &amp;yuml;,ÿ &amp;para;,¶ study]]></article-title>
<source><![CDATA[J Natl Cancer Inst]]></source>
<year>1998</year>
<volume>90</volume>
<numero>9</numero>
<issue>9</issue>
<page-range>675-84</page-range></nlm-citation>
</ref>
<ref id="B5">
<label>5</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Bokemeyer]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Bondarenko]]></surname>
<given-names><![CDATA[I]]></given-names>
</name>
<name>
<surname><![CDATA[Makhson]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Hartmann]]></surname>
<given-names><![CDATA[JT]]></given-names>
</name>
<name>
<surname><![CDATA[Aparicio]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[de Braud]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer]]></article-title>
<source><![CDATA[J Clin Oncol]]></source>
<year>2009</year>
<volume>27</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>663-71</page-range></nlm-citation>
</ref>
<ref id="B6">
<label>6</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Van Cutsem]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Köhne]]></surname>
<given-names><![CDATA[CH]]></given-names>
</name>
<name>
<surname><![CDATA[Hitre]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Zaluski]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Chang Chien]]></surname>
<given-names><![CDATA[CR]]></given-names>
</name>
<name>
<surname><![CDATA[Makhson]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer]]></article-title>
<source><![CDATA[N Engl J Med]]></source>
<year>2009</year>
<volume>360</volume>
<numero>14</numero>
<issue>14</issue>
<page-range>1408-17</page-range></nlm-citation>
</ref>
<ref id="B7">
<label>7</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Popat]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Hubner]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Houlston]]></surname>
<given-names><![CDATA[RS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Systematic review of microsatellite instability and colorectal cancer prognosis]]></article-title>
<source><![CDATA[J Clin Oncol]]></source>
<year>2005</year>
<volume>23</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>609-18</page-range></nlm-citation>
</ref>
<ref id="B8">
<label>8</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Alexander]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Watanabe]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Wu]]></surname>
<given-names><![CDATA[TT]]></given-names>
</name>
<name>
<surname><![CDATA[Rashid]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Li]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Hamilton]]></surname>
<given-names><![CDATA[SR]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Histopathological identification of colon cancer with microsatellite instability]]></article-title>
<source><![CDATA[Am J Pathol]]></source>
<year>2001</year>
<volume>158</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>527-35</page-range></nlm-citation>
</ref>
<ref id="B9">
<label>9</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Meyers]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Wagner]]></surname>
<given-names><![CDATA[MW]]></given-names>
</name>
<name>
<surname><![CDATA[Hwang]]></surname>
<given-names><![CDATA[HS]]></given-names>
</name>
<name>
<surname><![CDATA[Kinsella]]></surname>
<given-names><![CDATA[TJ]]></given-names>
</name>
<name>
<surname><![CDATA[Boothman]]></surname>
<given-names><![CDATA[DA]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidinemediated cell death and cell cycle responses]]></article-title>
<source><![CDATA[Cancer Res]]></source>
<year>2001</year>
<volume>61</volume>
<numero>13</numero>
<issue>13</issue>
<page-range>5193-201</page-range></nlm-citation>
</ref>
<ref id="B10">
<label>10</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Sargent]]></surname>
<given-names><![CDATA[DJ]]></given-names>
</name>
<name>
<surname><![CDATA[Marsoni]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Thibodeau]]></surname>
<given-names><![CDATA[SN]]></given-names>
</name>
<name>
<surname><![CDATA[Labianca]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Hamilton]]></surname>
<given-names><![CDATA[SR]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Confirmation of deficient mismatch repair (dMMR) as a predictive marker for lack of benefit from 5-FU based chemotherapy in stage II and III colon cancer (CC) A pooled molecular reanalysis of randomized chemotherapy trials]]></article-title>
<collab>Monges VT et al</collab>
<source><![CDATA[J Clin Oncol]]></source>
<year>2008</year>
<volume>26</volume>
<numero>15</numero>
<issue>15</issue>
<page-range>4008</page-range></nlm-citation>
</ref>
<ref id="B11">
<label>11</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Samowitz]]></surname>
<given-names><![CDATA[WS]]></given-names>
</name>
<name>
<surname><![CDATA[Albertsen]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Herrick]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Levin]]></surname>
<given-names><![CDATA[TR]]></given-names>
</name>
<name>
<surname><![CDATA[Sweeney]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Murtaugh]]></surname>
<given-names><![CDATA[MA]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer]]></article-title>
<source><![CDATA[Gastroenterology]]></source>
<year>2005</year>
<volume>129</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>837-45</page-range></nlm-citation>
</ref>
<ref id="B12">
<label>12</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Karapetis]]></surname>
<given-names><![CDATA[CS]]></given-names>
</name>
<name>
<surname><![CDATA[Khambata-Ford]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Jonker]]></surname>
<given-names><![CDATA[DJ]]></given-names>
</name>
<name>
<surname><![CDATA[O&amp;apos;Callaghan]]></surname>
<given-names><![CDATA[CJ]]></given-names>
</name>
<name>
<surname><![CDATA[Tu]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Tebbutt]]></surname>
<given-names><![CDATA[NC]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Kras mutations and benefit from cetuximab in advanced colorectal cancer]]></article-title>
<source><![CDATA[N Engl J Med]]></source>
<year>2008</year>
<volume>359</volume>
<numero>17</numero>
<issue>17</issue>
<page-range>1757-65</page-range></nlm-citation>
</ref>
<ref id="B13">
<label>13</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Cohen]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Cervera]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Svrcek]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Pellat]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Dreyer]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[de Gramont]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[BRAF-Mutated Colorectal Cancer What Is the Optimal Strategy for Treatment?]]></article-title>
<source><![CDATA[Curr Treat Options Oncol]]></source>
<year>2017</year>
<volume>18</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>9</page-range></nlm-citation>
</ref>
<ref id="B14">
<label>14</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Yoon]]></surname>
<given-names><![CDATA[HH]]></given-names>
</name>
<name>
<surname><![CDATA[Tougeron]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Shi]]></surname>
<given-names><![CDATA[Q]]></given-names>
</name>
<name>
<surname><![CDATA[Alberts]]></surname>
<given-names><![CDATA[SR]]></given-names>
</name>
<name>
<surname><![CDATA[Mahoney]]></surname>
<given-names><![CDATA[MR]]></given-names>
</name>
<name>
<surname><![CDATA[Nelson]]></surname>
<given-names><![CDATA[GD]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance)]]></article-title>
<collab>Alliance for Clinical Trials in Oncology</collab>
<source><![CDATA[Clin Cancer Res]]></source>
<year>2014</year>
<volume>20</volume>
<numero>11</numero>
<issue>11</issue>
<page-range>3033-43</page-range></nlm-citation>
</ref>
<ref id="B15">
<label>15</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Blons]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Emile]]></surname>
<given-names><![CDATA[JF]]></given-names>
</name>
<name>
<surname><![CDATA[Le Malicot]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Julié]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Zaanan]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Tabernero]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Prognostic value of KRAS mutations in stage III colon cancer post hoc analysis of the PETACC8 phase III trial dataset.]]></article-title>
<source><![CDATA[Ann Oncol]]></source>
<year>2014</year>
<volume>25</volume>
<numero>12</numero>
<issue>12</issue>
<page-range>2378-85</page-range></nlm-citation>
</ref>
<ref id="B16">
<label>16</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[André]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Gramont]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Vernerey]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Chibaudel]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Bonnetain]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study]]></article-title>
<collab>Tijeras-Raballand A et al</collab>
<source><![CDATA[J Clin Oncol]]></source>
<year>2015</year>
<volume>33</volume>
<numero>35</numero>
<issue>35</issue>
<page-range>4176-87</page-range></nlm-citation>
</ref>
<ref id="B17">
<label>17</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Gavin]]></surname>
<given-names><![CDATA[PG]]></given-names>
</name>
<name>
<surname><![CDATA[Colangelo]]></surname>
<given-names><![CDATA[LH]]></given-names>
</name>
<name>
<surname><![CDATA[Fumagalli]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Tanaka]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Remillard]]></surname>
<given-names><![CDATA[MY]]></given-names>
</name>
<name>
<surname><![CDATA[Yothers]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Mutation profiling and microsatellite instability in stage II and III colon cancer an assessment of their prognostic and oxaliplatin predictive value]]></article-title>
<source><![CDATA[Clin Cancer Res]]></source>
<year>2012</year>
<volume>18</volume>
<numero>23</numero>
<issue>23</issue>
<page-range>6531-41</page-range></nlm-citation>
</ref>
<ref id="B18">
<label>18</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Devaud]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Gallinger]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Chemotherapy of MMR-deficient colorectal cancer]]></article-title>
<source><![CDATA[Fam Cancer]]></source>
<year>2013</year>
<volume>12</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>301-6</page-range></nlm-citation>
</ref>
<ref id="B19">
<label>19</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Lindor]]></surname>
<given-names><![CDATA[NM]]></given-names>
</name>
<name>
<surname><![CDATA[Burgart]]></surname>
<given-names><![CDATA[LJ]]></given-names>
</name>
<name>
<surname><![CDATA[Leontovich]]></surname>
<given-names><![CDATA[O]]></given-names>
</name>
<name>
<surname><![CDATA[Goldberg]]></surname>
<given-names><![CDATA[RM]]></given-names>
</name>
<name>
<surname><![CDATA[Cunningham]]></surname>
<given-names><![CDATA[JM]]></given-names>
</name>
<name>
<surname><![CDATA[Sargent]]></surname>
<given-names><![CDATA[DJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors]]></article-title>
<source><![CDATA[J Clin Oncol]]></source>
<year>2002</year>
<volume>20</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>1043-8</page-range></nlm-citation>
</ref>
<ref id="B20">
<label>20</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Gryfe]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Kim]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Hsieh]]></surname>
<given-names><![CDATA[ET]]></given-names>
</name>
<name>
<surname><![CDATA[Aronson]]></surname>
<given-names><![CDATA[MD]]></given-names>
</name>
<name>
<surname><![CDATA[Holowaty]]></surname>
<given-names><![CDATA[EJ]]></given-names>
</name>
<name>
<surname><![CDATA[Bull]]></surname>
<given-names><![CDATA[SB]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer]]></article-title>
<source><![CDATA[N Engl J Med]]></source>
<year>2000</year>
<volume>342</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>69-77</page-range></nlm-citation>
</ref>
<ref id="B21">
<label>21</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Chapusot]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Martin]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Puig]]></surname>
<given-names><![CDATA[PL]]></given-names>
</name>
<name>
<surname><![CDATA[Ponnelle]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Cheynel]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Bouvier]]></surname>
<given-names><![CDATA[AM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[What is the best way to assess microsatellite instability status in colorectal cancer Study on a population base of 462 colorectal cancers]]></article-title>
<source><![CDATA[Am J Surg Pathol]]></source>
<year>2004</year>
<volume>28</volume>
<numero>12</numero>
<issue>12</issue>
<page-range>1553-9</page-range></nlm-citation>
</ref>
<ref id="B22">
<label>22</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Zeinalian]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Hashemzadeh-Chaleshtori]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Salehi]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Emami]]></surname>
<given-names><![CDATA[MH]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Clinical Aspects of Microsatellite Instability Testing in Colorectal Cancer]]></article-title>
<source><![CDATA[Adv Biomed Res]]></source>
<year>2018</year>
<volume>7</volume>
<numero>28</numero>
<issue>28</issue>
<page-range>28</page-range></nlm-citation>
</ref>
<ref id="B23">
<label>23</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ryan]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Sheahan]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Creavin]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Mohan]]></surname>
<given-names><![CDATA[HM]]></given-names>
</name>
<name>
<surname><![CDATA[Winter]]></surname>
<given-names><![CDATA[DC]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The current value of determining the mismatch repair status of colorectal cancer A rationale for routine testing]]></article-title>
<source><![CDATA[Crit Ver Oncol Hematol]]></source>
<year>2017</year>
<volume>116</volume>
<page-range>38-57</page-range></nlm-citation>
</ref>
<ref id="B24">
<label>24</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Meillan]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Vernerey]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Lefèvre]]></surname>
<given-names><![CDATA[JH]]></given-names>
</name>
<name>
<surname><![CDATA[Manceau]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Svrcek]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Augustin]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Mismatch Repair System Deficiency is associated with response to neoadjuvant chemoradiation in locally advanced rectal cancer]]></article-title>
<source><![CDATA[Int J Radiat Oncol Biol Phys]]></source>
<year>2019</year>
<volume>105</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>824-33</page-range></nlm-citation>
</ref>
<ref id="B25">
<label>25</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[McGranahan]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Swanton]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Clonal Heterogeneity and Tumor Evolution Past, Present, and the Future]]></article-title>
<source><![CDATA[Cell]]></source>
<year>2017</year>
<volume>168</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>613-28</page-range></nlm-citation>
</ref>
<ref id="B26">
<label>26</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Bhullar]]></surname>
<given-names><![CDATA[DS]]></given-names>
</name>
<name>
<surname><![CDATA[Barriuso]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Mullamitha]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Saunders]]></surname>
<given-names><![CDATA[MP]]></given-names>
</name>
<name>
<surname><![CDATA[Dwyer]]></surname>
<given-names><![CDATA[ST]]></given-names>
</name>
<name>
<surname><![CDATA[Aziz]]></surname>
<given-names><![CDATA[O]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Biomarker concordance between primary colorectal cancer and its metastases]]></article-title>
<source><![CDATA[EBioMedicine]]></source>
<year>2019</year>
<volume>40</volume>
<numero>40</numero>
<issue>40</issue>
<page-range>363-74</page-range></nlm-citation>
</ref>
<ref id="B27">
<label>27</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Marusyk]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Almendro]]></surname>
<given-names><![CDATA[V]]></given-names>
</name>
<name>
<surname><![CDATA[Polyak]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Intra-tumour heterogeneity a looking glass for cancer?]]></article-title>
<source><![CDATA[Nat Rev Cancer]]></source>
<year>2012</year>
<volume>12</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>323-34</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
