Paraf François
Service d'anatomie pathologique, Centre hospitalier universitaire Dupuytren, 2 avenue Martin Luther King, 87042 Limoges, et EA 4021, faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges.
Ann Pathol. 2007 Dec;27(6):433-8. doi: 10.1016/S0242-6498(07)71415-3.
Hereditary non polyposis colorectal cancer or Lynch syndrome is due to germline mutation of one the DNA mismatch repair genes. This mutation is associated with an unstable phenotype in tumor DNA characterized by new microsatellite alleles that are absent in matching normal DNA. Besides the Bethesda reference panel, a new panel of 5 mononucleotide microsatellites (BAT25, BAT26, NR21, NR24, NR27) has been proposed, which is more sensitive and faster to use in a multiplex PCR assay. In tumor cells, immunohistochemistry detects the loss of expression of either MLH1, MSH2, MSH6 or PMS2 protein, corresponding to the mutated gene. Immunohistochemistry guides germline analysis, except for MLH1 extinction which may correspond to either MLH1 germline mutation or methylation of MLH1 promoter resulting in inactivation. The latter is mostly due to aging and is often associated to the V600E BRAF gene mutation in tumor DNA. Combination of these 3 somatic analyses should reduce indications of germline mutation analysis in Lynch syndrome.
遗传性非息肉病性结直肠癌或林奇综合征是由一种DNA错配修复基因的种系突变引起的。这种突变与肿瘤DNA中的不稳定表型相关，其特征是在匹配的正常DNA中不存在的新微卫星等位基因。除了贝塞斯达参考面板外，还提出了一组新的5个单核苷酸微卫星（BAT25、BAT26、NR21、NR24、NR27），在多重PCR分析中使用起来更灵敏、更快。在肿瘤细胞中，免疫组织化学检测与突变基因相对应的MLH1、MSH2、MSH6或PMS2蛋白表达缺失。免疫组织化学指导种系分析，但MLH1缺失除外，它可能对应于MLH1种系突变或MLH1启动子甲基化导致的失活。后者主要归因于衰老，并且通常与肿瘤DNA中的V600E BRAF基因突变相关。这三种体细胞分析的组合应减少林奇综合征中种系突变分析的指征。
