Jacobs Michelle F, Murad Andrea M, Cho Nicole D, Cha Kelly B, Stoffel Elena M, Else Tobias
Division of Genetic Medicine, Department of Internal Medicine Cancer Genetics Clinic, Michigan Medicine, University of Michigan, Ann Arbor, Michigan
Department of Dermatology, University of Michigan, Ann Arbor, Michigan
cancer predisposition is characterized by an increased risk of developing multiple cutaneous melanomas, pancreatic cancer, and other tumors including gliomas and astrocytomas. Some affected individuals have a high total nevus count (often >50 nevi) and atypical-appearing nevi, although the number and extent of atypical nevi can vary significantly.
DIAGNOSIS/TESTING: The diagnosis of cancer predisposition is established in a proband by identification of a heterozygous germline pathogenic variant in by molecular genetic testing.
Standard treatment for melanoma, pancreatic cancer, and other cancers. Dermatologic examination for melanoma every six months; monthly self-skin examinations; annual alternating magnetic resonance cholangiopancreatography and endoscopic ultrasound starting at age 40 years or 10 years younger than the earliest exocrine pancreatic cancer diagnosis in the family, whichever is earlier; full-body and brain MRI in those with a pathogenic variant affecting the p14 isoform in the setting of a family history of nervous system tumors. Ultraviolet light exposure, particularly sunburns and tanning booths; tobacco use. Molecular genetic testing for the familial pathogenic variant is recommended for at-risk relatives of an affected individual. Family members who have a pathogenic variant should be offered regular lifelong surveillance. At-risk family members whose genetic status is unknown should undergo skin exams at their well child / health maintenance visits.
cancer predisposition is inherited in an autosomal dominant manner. The majority of individuals diagnosed with cancer predisposition inherited the germline pathogenic variant from a parent. A parent with a pathogenic variant may or may not have had a cancer diagnosis. Each child of an individual with cancer predisposition has a 50% chance of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, predictive testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.
癌症易感性的特点是发生多发性皮肤黑色素瘤、胰腺癌以及包括神经胶质瘤和星形细胞瘤在内的其他肿瘤的风险增加。一些受影响个体的痣总数较高（通常>50颗痣）且痣外观不典型，尽管不典型痣的数量和范围可能有很大差异。
诊断/检测：通过分子遗传学检测在先证者中鉴定出杂合种系致病变异，从而确立癌症易感性的诊断。
黑色素瘤、胰腺癌和其他癌症的标准治疗。每六个月进行一次黑色素瘤的皮肤科检查；每月进行一次自我皮肤检查；从40岁开始或比家族中最早诊断出的外分泌性胰腺癌早10年开始，每年交替进行磁共振胰胆管造影和内镜超声检查，以较早者为准；对于有影响p14异构体的致病变异且有神经系统肿瘤家族史的患者，进行全身和脑部MRI检查。避免紫外线暴露，尤其是晒伤和晒黑床；避免吸烟。建议对受影响个体的高危亲属进行家族性致病变异的分子遗传学检测。携带致病变异的家庭成员应接受定期的终身监测。遗传状态未知的高危家庭成员应在其儿童健康/健康维护就诊时进行皮肤检查。
癌症易感性以常染色体显性方式遗传。大多数被诊断为癌症易感性的个体从父母那里遗传了种系致病变异。携带致病变异的父母可能已被诊断患有癌症，也可能没有。患有癌症易感性的个体的每个孩子都有50%的机会遗传致病变异。一旦在受影响的家庭成员中鉴定出致病变异，就可以对高危亲属进行预测性检测以及进行产前/植入前基因检测。
