<?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>0034-8376</journal-id>
<journal-title><![CDATA[Revista de investigación clínica]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. invest. clín.]]></abbrev-journal-title>
<issn>0034-8376</issn>
<publisher>
<publisher-name><![CDATA[Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0034-83762020000600337</article-id>
<article-id pub-id-type="doi">10.24875/ric.20000111</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Complete Screening of Exons 2, 3, and 4 of KRAS and NRAS Genes Reveals a Higher Number of Clinically Relevant Mutations than Food and Drug Administration Quantitative Polymerase Chain Reaction-Based Commercial Kits]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sánchez-Ibarra]]></surname>
<given-names><![CDATA[Héctor E.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Reyes-Cortes]]></surname>
<given-names><![CDATA[Luisa M.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[López-Tavera]]></surname>
<given-names><![CDATA[Esteban]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Luna-Aguirre]]></surname>
<given-names><![CDATA[Claudia M.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Barrera-Saldaña]]></surname>
<given-names><![CDATA[Hugo A.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Vitagénesis SA de CV Genetics Laboratory ]]></institution>
<addr-line><![CDATA[Monterrey NL]]></addr-line>
<country>Mexico</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2020</year>
</pub-date>
<volume>72</volume>
<numero>6</numero>
<fpage>337</fpage>
<lpage>343</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S0034-83762020000600337&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S0034-83762020000600337&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S0034-83762020000600337&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract  Background: The presence of clinically relevant mutations in KRAS and NRAS genes determines the response of anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer (mCRC). The only quantitative polymerase chain reaction (qPCR)-based diagnostic tests approved by the Food and Drug Administration (FDA) screen merely for mutations in codons 12 and 13 of KRAS.  Objective: The objective of the study was to study the frequency of clinically relevant mutations in KRAS and NRAS genes that are not included in FDA-approved qPCR tests.  Methods: Formalin-fixed paraffin-embedded tumor specimens from 1113 mCRC Mexican patients from different health institutions across the country were analyzed by Sanger sequencing for KRAS mutations in exons 2, 3, and 4. Furthermore, 83 were analyzed in exons 2, 3, and 4 of NRAS.  Results: From the specimens tested for KRAS, 33.69% harbored a mutation. From these, 71.77% were in codon 12 and 27.69% in codon 13 (both located in exon 2). Codons 59 (exon 3) and 146 (exon 4) accounted for the remaining 0.54%. From the 83 specimens, in which NRAS was analyzed, three mutations were found in codon 12 (3.61%). Approximately 6% of RAS mutated specimens would have been falsely reported as RAS wild type if an FDA-approved qPCR diagnostic test had been used.  Conclusions: While these kits based on qPCR can be very practical and highly sensitive, their mutation coverage ignores mutations from poorly genetically characterized populations.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Colorectal cancer]]></kwd>
<kwd lng="en"><![CDATA[Molecular diagnostics]]></kwd>
<kwd lng="en"><![CDATA[RAS genes]]></kwd>
<kwd lng="en"><![CDATA[Real-time polymerase chain reaction]]></kwd>
<kwd lng="en"><![CDATA[Sanger sequencing]]></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[Ferlay]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Colombet]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Soerjomataram]]></surname>
<given-names><![CDATA[I]]></given-names>
</name>
<name>
<surname><![CDATA[Mathers]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Parkin]]></surname>
<given-names><![CDATA[DM]]></given-names>
</name>
<name>
<surname><![CDATA[Piñeros]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Estimating the global cancer incidence and mortality in 2018:GLOBOCAN sources and methods]]></article-title>
<source><![CDATA[Int J Cancer]]></source>
<year>2015</year>
<volume>136</volume>
<page-range>359-86</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[de la Chapelle]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Genetic predisposition to colorectal cancer]]></article-title>
<source><![CDATA[Nat Rev Cancer]]></source>
<year>2004</year>
<volume>4</volume>
<page-range>769-80</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[Smith]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Bounds]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Wolf]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Steele]]></surname>
<given-names><![CDATA[RJ]]></given-names>
</name>
<name>
<surname><![CDATA[Carey]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Wolf]]></surname>
<given-names><![CDATA[CR]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Activating K-ras mutations out with “hotspot”codons in sporadic colorectal tumours:implications for personalised cancer medicine]]></article-title>
<source><![CDATA[Br J Cancer]]></source>
<year>2010</year>
<volume>102</volume>
<page-range>693-703</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[Martinez-Garza]]></surname>
<given-names><![CDATA[SG]]></given-names>
</name>
<name>
<surname><![CDATA[Núñez-Salazar]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Calderon-Garcidueñas]]></surname>
<given-names><![CDATA[AL]]></given-names>
</name>
<name>
<surname><![CDATA[Bosques-Padilla]]></surname>
<given-names><![CDATA[FJ]]></given-names>
</name>
<name>
<surname><![CDATA[Niderhauser-García]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Barrera-Saldaña]]></surname>
<given-names><![CDATA[HA]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Frequency and clinicopathology associations of K-ras mutations in colorectal cancer in a Northeast Mexican population]]></article-title>
<source><![CDATA[Dig Dis]]></source>
<year>1999</year>
<volume>17</volume>
<page-range>225-9</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[Jiang]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Kimchi]]></surname>
<given-names><![CDATA[ET]]></given-names>
</name>
<name>
<surname><![CDATA[Staveley-O'Carroll]]></surname>
<given-names><![CDATA[KF]]></given-names>
</name>
<name>
<surname><![CDATA[Cheng]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Ajani]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Assessment of K-ras mutation:a step toward personalized medicine for patients with colorectal cancer]]></article-title>
<source><![CDATA[Cancer]]></source>
<year>2009</year>
<volume>115</volume>
<page-range>3609-17</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[Mcneil]]></surname>
<given-names><![CDATA[BC]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[K-ras mutations are changing practice in advanced colorectal cancer]]></article-title>
<source><![CDATA[J Natl Cancer Inst]]></source>
<year>2008</year>
<volume>100</volume>
<page-range>1667-9</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[Wójcik]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Kulig]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Oko]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Zazula]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Modzioch]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Niepsuj]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[KRAS mutation profile in colorectal carcinoma and novel mutation internal tandem duplication in KRAS]]></article-title>
<source><![CDATA[Polish J Pathol]]></source>
<year>2008</year>
<volume>59</volume>
<page-range>93-6</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[Tan]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Du]]></surname>
<given-names><![CDATA[X]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[KRAS mutation testing in metastatic colorectal cancer]]></article-title>
<source><![CDATA[World J Gastroenterol]]></source>
<year>2012</year>
<volume>18</volume>
<page-range>5171-80</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[Cárdenas-Ramos]]></surname>
<given-names><![CDATA[SG]]></given-names>
</name>
<name>
<surname><![CDATA[Alcázar-González]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Reyes-Cortés]]></surname>
<given-names><![CDATA[LM]]></given-names>
</name>
<name>
<surname><![CDATA[Torres-Grimaldo]]></surname>
<given-names><![CDATA[AA]]></given-names>
</name>
<name>
<surname><![CDATA[Calderón-Garcidueñas]]></surname>
<given-names><![CDATA[AL]]></given-names>
</name>
<name>
<surname><![CDATA[Morales-Casas]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The frequency and type of K-RAS mutations in Mexican patients with colorectal cancer]]></article-title>
<source><![CDATA[Am J Clin Oncol]]></source>
<year>2017</year>
<volume>40</volume>
<page-range>274-6</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[Downward]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Targeting RAS signalling pathways in cancer therapy]]></article-title>
<source><![CDATA[Nat Rev Cancer]]></source>
<year>2003</year>
<volume>3</volume>
<page-range>11-22</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[Sjöblom]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Jones]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Wood]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Parsons]]></surname>
<given-names><![CDATA[DW]]></given-names>
</name>
<name>
<surname><![CDATA[Lin]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Barber]]></surname>
<given-names><![CDATA[TD]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The consensus coding sequences of human breast and colorectal cancers]]></article-title>
<source><![CDATA[Science]]></source>
<year>2006</year>
<volume>314</volume>
<page-range>268-74</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[Martin]]></surname>
<given-names><![CDATA[TD]]></given-names>
</name>
<name>
<surname><![CDATA[Samuel]]></surname>
<given-names><![CDATA[JC]]></given-names>
</name>
<name>
<surname><![CDATA[Routh]]></surname>
<given-names><![CDATA[ED]]></given-names>
</name>
<name>
<surname><![CDATA[Der]]></surname>
<given-names><![CDATA[CJ]]></given-names>
</name>
<name>
<surname><![CDATA[Yeh]]></surname>
<given-names><![CDATA[JJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Activation and involvement of ral GTPases in colorectal cancer]]></article-title>
<source><![CDATA[Cancer Res]]></source>
<year>2011</year>
<volume>71</volume>
<page-range>206-15</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[Shi]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Washington]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Molecular testing in colorectal cancer:diagnosis of lynch syndrome and personalized cancer medicine]]></article-title>
<source><![CDATA[Am J Clin Pathol]]></source>
<year>2012</year>
<volume>137</volume>
<page-range>847-59</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[Vaughn]]></surname>
<given-names><![CDATA[CP]]></given-names>
</name>
<name>
<surname><![CDATA[Zobell]]></surname>
<given-names><![CDATA[SD]]></given-names>
</name>
<name>
<surname><![CDATA[Furtado]]></surname>
<given-names><![CDATA[LV]]></given-names>
</name>
<name>
<surname><![CDATA[Baker]]></surname>
<given-names><![CDATA[CL]]></given-names>
</name>
<name>
<surname><![CDATA[Samowitz]]></surname>
<given-names><![CDATA[WS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer]]></article-title>
<source><![CDATA[Genes Chromosom Cancer]]></source>
<year>2011</year>
<volume>50</volume>
<page-range>307-12</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[Andreyev]]></surname>
<given-names><![CDATA[HJ]]></given-names>
</name>
<name>
<surname><![CDATA[Norman]]></surname>
<given-names><![CDATA[R]]></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[P]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Kirsten ras mutations in patients with colorectal cancer:the multicenter “RASCAL”study]]></article-title>
<source><![CDATA[J Natl Cancer Inst]]></source>
<year>1998</year>
<volume>90</volume>
<page-range>675-84</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[Arrington]]></surname>
<given-names><![CDATA[AK]]></given-names>
</name>
<name>
<surname><![CDATA[Heinrich]]></surname>
<given-names><![CDATA[EL]]></given-names>
</name>
<name>
<surname><![CDATA[Lee]]></surname>
<given-names><![CDATA[W]]></given-names>
</name>
<name>
<surname><![CDATA[Duldulao]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Patel]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Sanchez]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Prognostic and predictive roles of KRAS mutation in colorectal cancer]]></article-title>
<source><![CDATA[Int J Mol Sci]]></source>
<year>2012</year>
<volume>13</volume>
<page-range>12153-68</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[Khoo]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Rogers]]></surname>
<given-names><![CDATA[TM]]></given-names>
</name>
<name>
<surname><![CDATA[Fellowes]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Bell]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Fox]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Molecular methods for somatic mutation testing in lung adenocarcinoma:EGFR and beyond]]></article-title>
<source><![CDATA[Transl Lung Cancer Res]]></source>
<year>2015</year>
<volume>4</volume>
<page-range>126-41</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[Jancik]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Drabek]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Berkovcova]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Xu]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Stankova]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Klein]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[A comparison of direct sequencing, pyrosequencing, high resolution melting analysis, TheraScreen DxS, and the K-ras StripAssay for detecting KRAS mutations in non small-cell lung carcinomas]]></article-title>
<source><![CDATA[J Exp Clin Cancer Res]]></source>
<year>2012</year>
<volume>31</volume>
<page-range>79</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[Neumann]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Zeindl-Eberhart]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Kirchner]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Jung]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer]]></article-title>
<source><![CDATA[Pathol Res Pract]]></source>
<year>2009</year>
<volume>205</volume>
<page-range>858-62</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[Bosch]]></surname>
<given-names><![CDATA[TM]]></given-names>
</name>
<name>
<surname><![CDATA[Meijerman]]></surname>
<given-names><![CDATA[I]]></given-names>
</name>
<name>
<surname><![CDATA[Beijnen]]></surname>
<given-names><![CDATA[JH]]></given-names>
</name>
<name>
<surname><![CDATA[Schellens]]></surname>
<given-names><![CDATA[JH]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer]]></article-title>
<source><![CDATA[Clin Pharmacokinet]]></source>
<year>2006</year>
<volume>45</volume>
<page-range>253-85</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[Sauna]]></surname>
<given-names><![CDATA[ZE]]></given-names>
</name>
<name>
<surname><![CDATA[Kimchi-Sarfaty]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Ambudkar]]></surname>
<given-names><![CDATA[SV]]></given-names>
</name>
<name>
<surname><![CDATA[Gottesman]]></surname>
<given-names><![CDATA[MM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Silent polymorphisms speak:how they affect pharmacogenomics and the treatment of cancer]]></article-title>
<source><![CDATA[Should synonymous single-nucleotide polymorphisms be ignored?Cancer Res]]></source>
<year>2007</year>
<volume>67</volume>
<page-range>9609-12</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[Supek]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Miñana]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Valcárcel]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Gabaldón]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Lehner]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Synonymous mutations frequently act as driver mutations in human cancers]]></article-title>
<source><![CDATA[Cell]]></source>
<year>2014</year>
<volume>156</volume>
<page-range>1324-35</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[Dong]]></surname>
<given-names><![CDATA[LQ]]></given-names>
</name>
<name>
<surname><![CDATA[Shi]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Ma]]></surname>
<given-names><![CDATA[LJ]]></given-names>
</name>
<name>
<surname><![CDATA[Yang]]></surname>
<given-names><![CDATA[LX]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[XY]]></given-names>
</name>
<name>
<surname><![CDATA[Zhang]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Spatial and temporal clonal evolution of intrahepatic cholangiocarcinoma]]></article-title>
<source><![CDATA[J Hepatol]]></source>
<year>2018</year>
<volume>69</volume>
<page-range>89-98</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[Therkildsen]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Bergmann]]></surname>
<given-names><![CDATA[TK]]></given-names>
</name>
<name>
<surname><![CDATA[Henrichsen-Schnack]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Ladelund]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Nilbert]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer:a systematic review and meta-analysis]]></article-title>
<source><![CDATA[Acta Oncol (Madr)]]></source>
<year>2014</year>
<volume>53</volume>
<page-range>852-64</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[Shen]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Han]]></surname>
<given-names><![CDATA[X]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Yang]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Lu]]></surname>
<given-names><![CDATA[SH]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Prognostic impact of mutation profiling in patients with stage II and III colon cancer]]></article-title>
<source><![CDATA[Sci Rep]]></source>
<year>2016</year>
<volume>6</volume>
<page-range>1-7</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[Dietrich]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Uhl]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Sailer]]></surname>
<given-names><![CDATA[V]]></given-names>
</name>
<name>
<surname><![CDATA[Holmes]]></surname>
<given-names><![CDATA[EE]]></given-names>
</name>
<name>
<surname><![CDATA[Jung]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Meller]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Improved PCR performance using template DNA from formalin-fixed and paraffin-embedded tissues by overcoming PCR inhibition]]></article-title>
<source><![CDATA[PLoS One]]></source>
<year>2013</year>
<volume>8</volume>
</nlm-citation>
</ref>
<ref id="B27">
<label>27</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ogino]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Kawasaki]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Brahmandam]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Yan]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Cantor]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Nangyal]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Sensitive sequencing method for KRAS mutation detection by pyrosequencing]]></article-title>
<source><![CDATA[J Mol Diagn]]></source>
<year>2005</year>
<volume>7</volume>
<page-range>413-21</page-range></nlm-citation>
</ref>
<ref id="B28">
<label>28</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Lee]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Brophy]]></surname>
<given-names><![CDATA[VH]]></given-names>
</name>
<name>
<surname><![CDATA[Cao]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Velez]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Hoeppner]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Soviero]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Analytical performance of a PCR assay for the detection of KRAS mutations (codons 12/13 and 61) in formalin-fixed paraffin-embedded tissue samples of colorectal carcinoma]]></article-title>
<source><![CDATA[Virchows Arch]]></source>
<year>2012</year>
<volume>460</volume>
<page-range>141-9</page-range></nlm-citation>
</ref>
<ref id="B29">
<label>29</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Jiang]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Huang]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Morehouse]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Zhu]]></surname>
<given-names><![CDATA[W]]></given-names>
</name>
<name>
<surname><![CDATA[Korolevich]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Sui]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Low frequency KRAS mutations in colorectal cancer patients and the presence of multiple mutations in oncogenic drivers in non-small cell lung cancer patients]]></article-title>
<source><![CDATA[Cancer Genet]]></source>
<year>2013</year>
<volume>206</volume>
<page-range>330-9</page-range></nlm-citation>
</ref>
<ref id="B30">
<label>30</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Tougeron]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Lecomte]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Pagès]]></surname>
<given-names><![CDATA[JC]]></given-names>
</name>
<name>
<surname><![CDATA[Villalva]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Collin]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Ferru]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Effect of low-frequency KRAS mutations on the response to anti-EGFR therapy in metastatic colorectal cancer]]></article-title>
<source><![CDATA[Ann Oncol]]></source>
<year>2013</year>
<volume>24</volume>
<page-range>1267-73</page-range></nlm-citation>
</ref>
<ref id="B31">
<label>31</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Netzel]]></surname>
<given-names><![CDATA[BC]]></given-names>
</name>
<name>
<surname><![CDATA[Grebe]]></surname>
<given-names><![CDATA[SK]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Companion-diagnostic testing limited to KRAS codons 12 and 13 misses 17% of potentially relevant RAS mutations in colorectal cancer]]></article-title>
<source><![CDATA[Clin Chim Acta]]></source>
<year>2013</year>
<volume>425</volume>
<page-range>1-2</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
