Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, 6120 Executive Boulevard, EPS 7101, Rockville, MD 20852-7231, USA.
Cancer Causes Control. 2009 Dec;20(10):2009-20. doi: 10.1007/s10552-009-9395-y.
Tumorigenesis is a multi-step process due to an accumulation of genetic mutations in multiple genes in diverse pathways which ultimately lead to loss of control over cell growth. It is well known that inheritance of rare germline mutations in genes involved in tumorigenesis pathways confer high lifetime risk of neoplasia in affected individuals. Furthermore, a substantial number of multiple malformation syndromes include cancer susceptibility in their phenotype. Studies of the mechanisms underlying these inherited syndromes have added to the understanding of both normal development and the pathophysiology of carcinogenesis. Myotonic dystrophy (DM) represents a group of autosomal dominant, multisystemic diseases that share the clinical features of myotonia, muscle weakness, and early-onset cataracts. Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) result from unstable nucleotide repeat expansions in their respective genes. There have been multiple reports of tumors in individuals with DM, most commonly benign calcifying cutaneous tumors known as pilomatricomas. We provide a summary of the tumors reported in DM and a hypothesis for a possible mechanism of tumorigenesis. We hope to stimulate further study into the potential role of DM genes in tumorigenesis, and help define DM pathogenesis, and facilitate developing novel treatment modalities.
肿瘤发生是一个多步骤的过程，由于多种途径中多个基因的遗传突变积累，最终导致细胞生长失控。众所周知，肿瘤发生途径中罕见的种系基因突变的遗传会使受影响个体的肿瘤发生终生风险增加。此外，大量的多发畸形综合征在其表型中包括癌症易感性。对这些遗传性综合征背后机制的研究增加了对正常发育和癌症发生的病理生理学的理解。肌强直性营养不良（DM）代表一组常染色体显性、多系统疾病，具有肌强直、肌肉无力和早发性白内障的临床特征。肌强直性营养不良 1 型（DM1）和肌强直性营养不良 2 型（DM2）是由于其各自基因中的不稳定核苷酸重复扩展所致。已有多份关于 DM 个体中肿瘤的报告，最常见的是良性钙化皮肤肿瘤，称为毛母细胞瘤。我们总结了 DM 中报告的肿瘤，并提出了肿瘤发生的可能机制假说。我们希望这能激发对 DM 基因在肿瘤发生中的潜在作用的进一步研究，帮助确定 DM 的发病机制，并促进新的治疗方式的开发。
