To evaluate and compare alterations detected by Alu-PCR, microsatellite instability (MI), and absence of hMLH1 and hMSH2 protein expression measured by immunohistochemical (IHC) analyses as features characteristic of hereditary nonpolyposis colorectal cancer (HNPCC).
Genetic diagnosis of high-penetrance susceptibility for colorectal cancer (CRC) is achievable for a high proportion of familial CRC by exome sequencing.
In this report we present data from a large series of families with HNPCC and indicate that there are subtle differences between families that harbor germline changes in hMSH2 and families that harbor hMLH1 mutations.
For patients with Lynch Syndrome (LS) (formerly known as hereditary nonpolyposis colorectal cancer or HNPCC), inheritance of one of several mutated mismatch repair genes (MMR) results in an increased risk for a variety of malignancies including colon, rectal, endometrial, urinary tract, gastric, small bowel and others [1].
We observed a significant difference in the CRC-free survival time between males and females, between MSH2 and MSH6 mutation carriers and between MLH1 and MSH6, indicating that this series is representative of Lynch syndrome.
The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2.
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited colorectal cancer syndrome attributable to mutations in one of several DNA mismatch repair genes, most commonly MLH1 and MSH2 .
Our results indicate that (1) MTS patients exhibit significantly more mutations in the hMSH2 gene than in the hMLH1 gene; and (2) the subpopulation of MTS patients who are also affected by colorectal cancer, irrespective of family history and age at onset of tumors, may have a likelihood for an underlying DNA MMR defect similar to that for patients with a family history fulfilling the strict clinical criteria for HNPCC.
Two (mismatch repair) genes (hMSH2 on chromosome 2p and hMLH1 on chromosome 3p) have recently been identified which appear to be involved in the development of cancer in most of the HNPCC families.
This article reviews the history of HNPCC, its clinical features, gene discovery, development of clinical genetic workup, and clinical surveillance, with an emphasis on the two major HNPCC genes, hMSH2 and hMLH1.
A type of hereditary colorectal cancer (CRC) known as hereditary nonpolyposis colorectal cancer (HNPCC) is associated with MLHI and MSH2 gene mutations.