Risk assessment and early detection strategies in individuals with BRCA1/2 mutations and with Lynch syndrome have been quite extensively studied, whereas much less is known about the management of mutation carriers with less common high-penetrance cancer susceptibility genes (PTEN, TP53, STK11, CDH1), and particularly those who carry mutations in moderate-penetrance genes (e.g., PALB2, CHEK2, ATM, NF1, RAD51C, RAD51D, BRIP1).
In this study, copy number variations (CNVs) were evaluated in 45 unrelated patients with clinical hypothesis of Lynch syndrome (Amsterdam or Bethesda criteria); negative for MLH1, MSH2, MSH6, PMS2, CHEK2*1100delC and TP53 pathogenic mutations; aiming to reveal new predisposing genes.
This study investigated whether TP53 polymorphisms are associated with colorectal cancer (CRC) in patients with Lynch syndrome and whether TP53 interacts with lifestyle factors to modify CRC risk.
HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of β-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients.
We have previously reported that the common, functionally different variants Arg72Pro in p53 and Arg462Gln in RNASEL are associated with the age of disease onset of colorectal cancer in Lynch syndrome patients.
We genotyped p53 codon 72 in 193 individuals with Lynch syndrome mutations, 93 patients with sporadic microsatellite unstable colorectal cancer, and 93 patients with sporadic microsatellite stable colorectal cancer from Finland and 323 Finnish controls.
From the evidence that the DNA mismatch repair system and p53 interact to maintain genomic integrity, we hypothesized that the codon 72 variation may influence the age of onset of disease in HNPCC patients.
All of the three hereditary tumors from hereditary nonpolyposis colorectal cancer (HNPCC) patients were MSI-H. MSI-H tumors were significantly associated with poor differentiation and the presence of wild-type K-RAS and p53 genes.
To understand the roles of these genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesis, we examined whether BAX mutations occur in adenoma and carcinoma specimens from patients with HNPCC and also determined the frequencies of p53 mutations.