A frameshift mutation in exon 19 of MLH1 in a Chinese Lynch syndrome family: a pedigree study

Lynch syndrome (LS),an autosomal dominantly inherited disease previously known as hereditary non-polyposis coloreetal cancer (HNPCC),leads to a high risk of colorectal cancer (CRC)as well as malignancy at certain sites including endometrium,ovary,stomach,and small bowel (Hampel et al.,2008;Lynch et al.,2009).Clinically,LS is considered the most common hereditary CRC-predisposing syndrome, accounting for about 3% of all CRC cases (Popat et al., 2005).LS is associated with mutations of DNA mismatch repair (MMR)genes such as MLH1,MSH2, MSH6,PMS2,and EPCAM (Ligtenberg et al.,2009;Lynch et al.,2009),which can trigger a high frequency of replication errors in both microsatellite regions and repetitive sequences in the coding regions of various cancer-related genes.

Low prevalence of mismatch repair deficiency in Chinese colorectal cancers:a multicenter study

Background:Although universal testing for mismatch repair deficiency(dMMR)has been recommended to all colorectal cancer(CRC)patients,related evidence for the Chinese population is lacking.Here,we investigated the prevalence and clinicopathological features of dMMR patients in a large Chinese CRC cohort.Methods:We included 7,373 CRC patients treated at four Chinese medical centers between August 2010 and September 2016.Patients’baseline characteristics and pathological features were recorded.The clinicopathological features were compared between patients with MLH1/PMS2 deficiency(dMLH1/PMS2)and MSH2/MSH6 deficiency(dMSH2/MSH6).Results:Among the investigated patients,654(8.9%)were identified with dMMR CRCs and,of them,401(61.3%)were males,with a median age of 55 years(range,22-87 years);355(54.3%)had stage II CRC based on American Joint Committee on Cancer 8th edition.The prevalence of the dMLH1/PMS2 group and the dMSH2/MSH6 group were 51.5%(337/654)and 25.1%(164/654),respectively.Compared with dMSH2/MSH6 patients,those with dMLH1/PMS2 were older(57 vs 52 years,P<0.001),more likely to be female(45.7%vs 31.5%,P=0.004),prone to having tumors located in the right-hand side of the colon(59.0%vs 47.6%,P=0.015),and less likely to have a family history of tumors(29.7%vs 43.3%,P=0.003).Conclusions:The prevalence of dMMR in Chinese CRC patients was low,especially in the dMLH1/PMS2 group.The clinicopathological features were different between dMMR subgroups.