The specific high-risk genes are BRCA1, BRCA2, RAD51C, RAD51D, and BRIP1, plus Lynch syndrome (MLH1, MSH2, MSH6, PMS1
, and EpCAM), and the minimum surgery for these women is a risk-reducing salpingo-oophorectomy (RRSO).
Genes Tested AtP ALK APC ATM BAP1 BRCA2 BRIP1 BUB1B CDC73 CDH1 CEP57 CHEK2 CYLD DDB2 DICER1 ERCC3 ERCC4 ERCC5 EXT1 EXT2 FANCD2 FANCE FANCF FANCG FANCI GATA2 GPC3 HNF1A HOXB13 HRAS MLH1 MHS2 MSH6 MUTYH NBN PHOX2B PMS1
PMS2 PPM1D PRF1 RAD51D RBI RECQL4 RET RHBDF2 SDHC SDHD SLX4 SMAD4 SMARCA4 TP53 TSC1 TSC2 VHL WT1 BARD1 BLM BMPR1A BRCA1 CDK4 CDKN1C CDKN2A CEBPA DI53L2 EGFR EPCAM ERCC2 EZH2 FANCA FANCB FANCC FANCL FANCM FH FLCN KIT MAX MEN1 MET NF1 NF2 NSD1 PALB2 PRKAR1A PTCH1 PTEN RAD51C RUN XI SBDS SDHAF2 SDHB SMARCB1 STK11 5UFU TMEM127 WRN XPA XPC This chart shows all 98 cancer susceptible genes included in this new test.
, and MSH2 interactions during the initiation of DNA mismatch repair in yeast.
Hasta el presente, se informan mas de 500 mutaciones diferentes en todos los genes MMR, sin embargo, no se ha encontrado asociacion entre las mutaciones en los genes PMS1
y PMS2 y el desarrollo del CCR.
2] Human genes: BRCA1, breast cancer 1, early onset; BRCA2, breast cancer 2, early onset; MGST3, microsomal glutathione S-transferase 3; GBP1, guanylate binding protein 1, interferon-inducible, 67kDa; MTAP, methylthioadenosine phosphorylase; GGH, gamma-glutamyl hydrolase (conjugase, folylpolygamma-glutamyl hydrolase); MADCAM1, mucosal vascular addressin cell adhesion molecule 1; POSTN, periostin, osteoblast specific factor; PMS1, PMS1 postmeiotic segregation increased 1 (S.
Gene Gene name US patent symbol MGST3 Microsomal glutathione S-transferase 3 5,919,627 GBP1 Guanylate binding protein 1, interferon- 6,894,157 inducible, 67kDa GGH Gamma-glutamyl hydrolase (conjugase, 5,801,031 folylpolygammaglutamyl hydrolase) MTAP Methylthioadenosine phosphorylase 5,942,393; 6,870,037 MADCAM1 Mucosal vascular addressin cell adhesion 7,750,137 molecule 1 POSTN Periostin, osteoblast specific factor 6,518,063 PMS1 PMS1 postmeiotic segregation increased 1 5,922,855; (S.
On the other hand, low-level microsatellite instability has not been associated with such mismatch repair gene alterations, although other mismatch repair genes such as PMS1
and MSH6 have not been studied.
In families with HNPCC, 214 different germline mutations have been described to date by direct sequence analysis: 127 mutations were located in the MLH1 gene and 81 in the MSH2 gene, whereas only 6 mutations were detected in the MSH6, the PMS1
, or the PMS2 gene (9).
93) Germline mutations of mismatch repair genes, including MLH1, MSH2, PMS1
, PMS2, and MSH6, are associated with HNPCC.
DNA repair defects are caused by mutations in genes responsible for the repair of base-base DNA mismatches (MLH1, MLH3, MSH2, MSH6, PMS1
Germline mutations in several human DNA mismatch repair genes, including MSH2, MLH1, PMS1
, PMS2, and MSH6/GTBP, have been identified in patients with hereditary nonpolyposis colorectal cancer (HNPCC).