Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for approximately 2% of all colorectal cancer (CRC) cases and is the most common hereditary CRC syndrome.
Synopsis
tumoral predisposition
- colorectal adenocarcinoma
- gastric carcinomas
- endometrial carcinoma (15823135)
-
cutaneous tumors
- sebaceous tumors (Muir-Torre syndrome)
cerebral tumors
DNA mismatch repair proteins
| MLH1 | MLH3 | MSH2 | MSH6 | PMS1 | PMS2 | TGFBR2 |
Pathology: HNPCC syndromes, mismatch repair deficiency
| Disease | Gene | MIM. | Loc. | MIM |
| HNPCC1 | MSH2 | MIM.609309 | 2p22-p21 | MIM.120435 |
| HNPCC2 | MLH1 | MIM.120436 | 3p21.3 | MIM.609310 |
| HNPCC3 | PMS1 | MIM.600258 | 2q31-q33 | MIM.600258 |
| HNPCC4 | PMS2 | MIM.600259 | 7p22 | MIM.600259 |
| HNPCC5 | MSH6 | MIM.600678 | 2p16 | MIM.600678 |
| HNPCC6 | TGFBR2 | MIM.190182 | 3p22 | MIM.190182 |
| HNPCC7 | MLH3 | MIM.604395 | 14q24.3 | MIM.604395 |
MSH2 and MLH1 mutations are found in approximately two-thirds of the Amsterdam-criteria-positive families and in much lower percentages of the Amsterdam-criteria-negative families.
In one series, 92%Amsterdam-criteria-positive families and 70% of the Amsterdam-criteria-negative families, a mutation was detected in one of three MMR genes: MSH2, MLH1, MSH6. 27% of the mutations were genomic rearrangements. (12658575)
Reviews
Umar A, Risinger JI, Hawk ET, Barrett JC. Testing guidelines for hereditary non-polyposis colorectal cancer. Nat Rev Cancer. 2004 Feb;4(2):153-8. PMID: 14964310
Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003 Mar 6;348(10):919-32. PMID: 12621137
References
Immunohistochemistry as first-line screening for detecting colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: a 2-antibody panel may be as predictive as a 4-antibody panel. Shia J, Tang LH, Vakiani E, Guillem JG, Stadler ZK, Soslow RA, Katabi N, Weiser MR, Paty PB, Temple LK, Nash GM, Wong WD, Offit K, Klimstra DS. Am J Surg Pathol. 2009 Nov;33(11):1639-45.PMID: 19701074