Watanabe Takafumi, Soeda Shu, Endo Yuta, Okabe Chikako, Sato Tetsu, Kamo Norihito, Ueda Makiko, Kojima Manabu, Furukawa Shigenori, Nishigori Hidekazu, Takahashi Toshifumi, Fujimori Keiya
Department of Obstetrics and Gynecology, Fukushima Medical University, Fukushima 960-1295, Japan.
Fukushima Medical Center for Children and Women, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
Int J Mol Sci. 2022 Jan 29;23(3):1563. doi: 10.3390/ijms23031563.
Hereditary cancer syndromes, which are characterized by onset at an early age and an increased risk of developing certain tumors, are caused by germline pathogenic variants in tumor suppressor genes and are mostly inherited in an autosomal dominant manner. Therefore, hereditary cancer syndromes have been used as powerful models to identify and characterize susceptibility genes associated with cancer. Furthermore, clarification of the association between genotypes and phenotypes in one disease has provided insights into the etiology of other seemingly different diseases. Molecular genetic discoveries from the study of hereditary cancer syndrome have not only changed the methods of diagnosis and management, but have also shed light on the molecular regulatory pathways that are important in the development and treatment of sporadic tumors. The main cancer susceptibility syndromes that involve gynecologic cancers include hereditary breast and ovarian cancer syndrome as well as Lynch syndrome. However, in addition to these two hereditary cancer syndromes, there are several other hereditary syndromes associated with gynecologic cancers. In the present review, we provide an overview of the clinical features, and discuss the molecular genetics, of four rare hereditary gynecological cancer syndromes; Cowden syndrome, Peutz-Jeghers syndrome, DICER1 syndrome and rhabdoid tumor predisposition syndrome 2.
遗传性癌症综合征的特征是发病年龄较早且患某些肿瘤的风险增加,由肿瘤抑制基因中的种系致病性变异引起,大多以常染色体显性方式遗传。因此,遗传性癌症综合征已被用作识别和表征与癌症相关的易感基因的有力模型。此外,阐明一种疾病的基因型与表型之间的关联,为其他看似不同的疾病的病因提供了见解。对遗传性癌症综合征的研究在分子遗传学上的发现不仅改变了诊断和管理方法,还揭示了在散发性肿瘤的发生和治疗中起重要作用的分子调控途径。涉及妇科癌症的主要癌症易感综合征包括遗传性乳腺癌和卵巢癌综合征以及林奇综合征。然而,除了这两种遗传性癌症综合征外,还有其他几种与妇科癌症相关的遗传性综合征。在本综述中,我们概述了四种罕见的遗传性妇科癌症综合征;考登综合征、黑斑息肉综合征、DICER1综合征和横纹肌瘤易感性综合征2的临床特征,并讨论了其分子遗传学。