title: Somatic c.34G>T KRAS mutation: a new prescreening test for MUTYH-associated polyposis?
abstract: We investigated the somatic c.34G>T KRAS transversion as a marker suggestive of MUTYH-associated polyposis (MAP). We compared 86 adenomas and 19 colorectal cancers (CRCs) of 30 MAP patients to 135 adenomas and five CRCs of 47 familial adenomatous polyposis (FAP) patients. The c.34G>T mutation was investigated by DNA sequencing. Secondly, the germline MUTYH gene sequence was analyzed in patients carrying c.34G>T in CRCs diagnosed between 2008 and 2012. The c.34G>T was present in 39.7% of MAP adenomas versus 1.6% of FAP adenomas (P < 0.01). Sensitivity and specificity for detecting MAP were 39.7% and 98%, respectively. Sensitivity increased with the number of adenomas tested (P = 0.039). KRAS exon 2 analysis was performed on 2239 CRC and 2.2% harbored the c.34G>T transversion. Among 28 carriers of the c.34G>T mutation, biallelic MUTYH mutations were detected in seven patients (25%). One patient did not have any polyp or family history and did not fulfill criteria for MUTYH testing. With high specificity, the c.34G>T mutation seems to be a useful and promising test for MAP. For polyposis, it may guide genetic testing toward APC or MUTYH. If routinely performed in CRC patients, it could help to diagnose MUTYH-mutation carriers, even when they don't fulfill genetic testing criteria.
authors.affiliation: Department of Digestive Surgery, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France; Department of Genetics, Hôpital de La Pitié Salpêtrière (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Aimé
authors.affiliation: Department of Genetics, Hôpital de La Pitié Salpêtrière (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Coulet
authors.affiliation: Department of Digestive Surgery, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France. Electronic address: jeremie.lefevre@sat.aphp.fr.
authors.forename: Jeremie H
authors.initials: JH
authors.lastname: Lefevre
authors.affiliation: Department of Genetics, Hôpital de La Pitié Salpêtrière (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Colas
authors.affiliation: Department of Pathology, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Cervera
authors.affiliation: Department of Pathology, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Flejou
authors.affiliation: Department of Molecular Biology, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lascols
authors.affiliation: Department of Genetics, Hôpital de La Pitié Salpêtrière (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Soubrier
authors.affiliation: Department of Digestive Surgery, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Parc
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012680:Sensitivity and Specificity; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: KRAS; MUTYH; MUTYH-associated polyposis; adenomatous polyposis; colorectal cancer