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

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

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