Thyroid and Breast Cancer in 2 Sisters With Monoallelie Mutations in the Ataxia Telangiectasia Mutated Gene

The presence of a bidirectional risk for metachronous carcinomas among women with thyroid and breast cancer is well established. However, the underlying risk factors remain poorly understood. Two sisters developed papillary thyroid cancer (PTC) at age 32 and 34 years, followed by ductal carcinoma of...

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Bibliographic Details
Published in:Journal of the Endocrine Society 2022-04, Vol.6 (4)
Main Authors: Miasaki, Fabiola Y, Saito, Kelly C, Yamamoto, Guilherme L, Boguszewski, Cesar L, de Carvalho, Gisah A, Kimura, Edna T, Kopp, Peter A
Format: Article
Language:English
Subjects:
Ataxia
Ataxia telangiectasia
Breast cancer
Cancer
Development and progression
Gene mutations
Genes
Genetic aspects
Lymphomas
Progesterone
Risk factors
Thyroid cancer
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Summary:The presence of a bidirectional risk for metachronous carcinomas among women with thyroid and breast cancer is well established. However, the underlying risk factors remain poorly understood. Two sisters developed papillary thyroid cancer (PTC) at age 32 and 34 years, followed by ductal carcinoma of the breast at 44 and 42 years. The 2 children of the younger sister developed ataxia-telangiectasia; the son also developed lymphoblastic lymphoma and his sister died secondary to acute lymphoblastic leukemia (ALL). They were found to be compound heterozygous for ataxia telangiectasia mutated (ATM) gene mutations (c.3848T>C, p.L1283P; and c.802C>T, p.Q268X). Exome sequencing of the 2 sisters (mother and aunt of the children with ataxia-telangiectasia) led to the detection of the pathogenic monoallelic ATM mutation in both of them (c.3848T>C; minor allele frequency [MAF] < 0.01) but detected no other variants known to confer a risk for PTC or breast cancer. The findings suggest that monoallelic ATM mutations, presumably in conjunction with additional genetic and/or nongenetic factors, can confer a risk for developing PTC and breast cancer. Key Words: thyroid cancer, breast neoplasms, ataxia telangiectasia, ATM protein, neoplastic syndromes, genetic predisposition to disease Abbreviations: ALL, acute lymphoblastic leukemia; ATM, ataxia telangiectasia mutated; CLS, Cowden-like syndrome; CS, Cowden syndrome; ER, estrogen receptor; FNMTC, familial non-medullary thyroid cancer; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor; PTC, papillary thyroid cancer.
ISSN:2472-1972
2472-1972
DOI:10.1210/jendso/bvac026