Felton K E A, Gilchrist D M, Andrew S E
Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
Clin Genet. 2007 Jun;71(6):499-500. doi: 10.1111/j.1399-0004.2007.00801.x.
Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome types I and II, and the related subtypes Turcot and Muir-Torre syndrome, have all been associated with inheritance of germ line mutations in the DNA mismatch repair (MMR) genes. Fifty individuals have recently been identified with an early onset of a different spectrum of cancers associated with inheritance of two MMR mutations--resulting either in a constitutive loss of MMR function, or greatly impaired MMR function. In contrast to Lynch I and II individuals, individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein, present with hematological and brain malignancies in the first decade of life. Biallelic mutations with compromised but residual protein function present with a broader spectrum of cancers (brain, hematological or gastrointestinal) in the second to fourth decades of life. We propose that inheritance of two MMR mutations in an individual and the unique tumor spectrum that occurs with an early onset should be defined separately from Lynch syndrome I and II, or the subtypes Turcot and Muir-Torre. We suggest Lynch III as an appropriate name for identifying individuals with constitutively compromised MMR associated with biallelic mutations.
遗传性非息肉病性结直肠癌（HNPCC），也被称为林奇综合征I型和II型，以及相关的亚型图尔科特综合征和穆尔-托里综合征，均与DNA错配修复（MMR）基因的种系突变遗传有关。最近已鉴定出50名个体，他们过早出现了一系列不同的癌症，这些癌症与两个MMR突变的遗传有关——导致MMR功能的组成性丧失或MMR功能严重受损。与林奇I型和II型个体不同，MMR基因中纯合或复合杂合突变的遗传导致蛋白质完全缺乏的个体，在生命的第一个十年出现血液系统和脑部恶性肿瘤。具有受损但仍有残余蛋白质功能的双等位基因突变的个体，在生命的第二个至第四个十年出现更广泛的癌症谱（脑、血液或胃肠道）。我们建议，个体中两个MMR突变的遗传以及过早出现的独特肿瘤谱应与林奇综合征I型和II型或图尔科特和穆尔-托里亚型分开定义。我们建议将林奇III型作为识别与双等位基因突变相关的组成性受损MMR个体的合适名称。
