Pattern of clinically relevant mutations in consecutive series of Russian colorectal cancer patients.
One hundred and ninety-five consecutive surgically treated Russian colorectal cancer (CRC) patients were retrospectively analyzed for the presence of mutations in KRAS, NRAS, BRAF and PIK3CA genes as well as for the microsatellite instability status. Comparison between high-resolution melting analysis, co-amplification at lower denaturation temperature PCR, DNA sequencing and allele-specific PCR for the detection of KRAS codon 12/13 mutations revealed that none of these methods alone provided satisfactory results in 100 % of the analyzed cases; this experience supports the use of more than one mutation-detecting technique at least in some circumstances. KRAS codon 12/13 substitutions were detected in 70 (35.9 %) CRC cases. Other mutations in the RAS/RAF genes occurred in 22 (11.3 %) cases and included rare KRAS (n = 6), NRAS (n = 8) and BRAF (n = 8) alterations. 5 BRAF mutations affected codon 600, while the remaining 3 potentially functional substitutions were located in the position 594. Twenty-four (12.3 %) CRC cases carried mutations in the PIK3CA, and 18 of these tumors also contained activating alteration in the RAS/RAF genes (p = 0.007). Only 3 (1.5 %) CRC cases showed high-level microsatellite instability (MSI-H) as determined by a panel of mononucleotide markers. Overall, the distribution of potentially predictive mutations in Russian CRC cases is similar to the one observed in other patient series of European descent. Noticeable occurrence of D594G mutation in BRAF oncogene and low frequency of MSI-H may deserve specific attention.
Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, St.-Petersburg, Russia.
Grigoriy A
GA
Yanus
Anna V
AV
Belyaeva
Alexandr O
AO
Ivantsov
Ekatherina Sh
ESh
Kuligina
Evgeny N
EN
Suspitsin
Natalia V
NV
Mitiushkina
Svetlana N
SN
Aleksakhina
Aglaya G
AG
Iyevleva
Olga A
OA
Zaitseva
Olga S
OS
Yatsuk
Tatiana V
TV
Gorodnova
Tatiana N
TN
Strelkova
Sofia A
SA
Efremova
Alla Yu
AY
Lepenchuk
Altn N
AN
Ochir-Garyaev
Moisey B
MB
Paneyah
Dmitriy E
DE
Matsko
Alexandr V
AV
Togo
Evgeny N
EN
Imyanitov
D058534:Class I Phosphatidylinositol 3-Kinases; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D020558:GTP Phosphohydrolases / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D053842:Microsatellite Instability; D009154:Mutation / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D012426:Russia; D018631:ras Proteins / Q000235:genetics
D003062:Codon; C117307:KRAS protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins