Spectrum of APC and MUTYH germ-line mutations in Russian patients with colorectal malignancies

Clin Genet. 2018 May;93(5):1015-1021. doi: 10.1111/cge.13228. Epub 2018 Mar 9.


Distribution of cancer-predisposing mutations demonstrates significant interethnic variations. This study aimed to evaluate patterns of APC and MUTYH germ-line mutations in Russian patients with colorectal malignancies. APC gene defects were identified in 26/38 (68%) subjects with colon polyposis; 8/26 (31%) APC mutations were associated with 2 known mutational hotspots (p.E1309Dfs*4 [n = 5] and p.Q1062fs* [n = 3]), while 6/26 (23%) mutations were novel (p.K73Nfs*6, p.S254Hfs*12, p.S1072Kfs*9, p.E1547Kfs*11, p.L1564X and p.C1263Wfs*22). Biallelic mutations in MUTYH gene were detected in 3/12 (25%) remaining subjects with polyposis and in 6/90 (6.7%) patients with colorectal cancer (CRC) carrying KRAS p.G12C substitution, but not in 231 early-onset CRC cases negative for KRAS p.G12C allele. In addition to known European founder alleles p.Y179C and p.G396D, this study revealed a recurrent character of MUTYH p.R245H germ-line mutation. Besides that, 3 novel pathogenic MUTYH alleles (p.L111P, p.R245S and p.Q293X) were found. Targeted next-generation sequencing of 7 APC/MUTYH mutation-negative DNA samples identified novel potentially pathogenic POLD1 variant (p.L460R) in 1 patient and known low-penetrant cancer-associated allele CHEK2 p.I157T in 3 patients. The analysis of 1120 healthy subjects revealed 15 heterozygous carriers of recurrent MUTYH mutations, thus the expected incidence of MUTYH-associated polyposis in Russia is likely to be 1:23 000.

Keywords: APC; CHEK2; MUTYH; MUTYH-associated polyposis (MAP); POLD1; colorectal neoplasms; familial adenomatous polyposis (FAP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Adult
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Glycosylases / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Germ-Line Mutation / genetics
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Russia / epidemiology


  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • DNA Glycosylases
  • mutY adenine glycosylase