Somatic c.34G>T KRAS mutation: a new prescreening test for MUTYH-associated polyposis?

Adeline Aimé; Florence Coulet; Jeremie H Lefevre; Chrystelle Colas; Pascale Cervera; Jean-François Flejou; Olivier Lascols; Florent Soubrier; Yann Parc

doi:10.1016/j.cancergen.2015.04.005

Somatic c.34G>T KRAS mutation: a new prescreening test for MUTYH-associated polyposis?

Cancer Genet. 2015 Jul-Aug;208(7-8):390-5. doi: 10.1016/j.cancergen.2015.04.005. Epub 2015 Apr 23.

Authors

Adeline Aimé¹, Florence Coulet², Jeremie H Lefevre³, Chrystelle Colas², Pascale Cervera⁴, Jean-François Flejou⁴, Olivier Lascols⁵, Florent Soubrier², Yann Parc⁶

Affiliations

¹ 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.
² Department of Genetics, Hôpital de La Pitié Salpêtrière (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
³ Department of Digestive Surgery, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France. Electronic address: jeremie.lefevre@sat.aphp.fr.
⁴ Department of Pathology, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
⁵ Department of Molecular Biology, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.
⁶ Department of Digestive Surgery, Hôpital Saint Antoine (Assistance Publique-Hôpitaux de Paris), Paris VI University, Paris, France.

PMID: 26056087
DOI: 10.1016/j.cancergen.2015.04.005

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.

Keywords: KRAS; MUTYH; MUTYH-associated polyposis; adenomatous polyposis; colorectal cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenomatous Polyposis Coli / diagnosis
Adenomatous Polyposis Coli / genetics*
Adult
Base Sequence
Colorectal Neoplasms / diagnosis
Colorectal Neoplasms / genetics*
DNA Glycosylases / genetics*
DNA Mutational Analysis
Gene Frequency
Genetic Predisposition to Disease / genetics
Genetic Testing
Genotype
Germ-Line Mutation
Humans
Middle Aged
Point Mutation*
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins p21(ras)
Sensitivity and Specificity
ras Proteins / genetics*

Substances

KRAS protein, human
Proto-Oncogene Proteins
DNA Glycosylases
mutY adenine glycosylase
Proto-Oncogene Proteins p21(ras)
ras Proteins