Familial Adrenocortical Carcinoma in Association With Lynch Syndrome
| Autor: | Benjamin G, Challis, Narayanan, Kandasamy, Andrew S, Powlson, Olympia, Koulouri, Anand Kumar, Annamalai, Lisa, Happerfield, Alison J, Marker, Mark J, Arends, Serena, Nik-Zainal, Mark, Gurnell |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities MutS Homolog 2 Protein Neoplastic Syndromes Hereditary Adrenocortical Carcinoma Humans Female Genetic Predisposition to Disease Genetic Testing Middle Aged Special Features Colorectal Neoplasms Hereditary Nonpolyposis Adrenal Cortex Neoplasms Germ-Line Mutation |
| Zdroj: | The Journal of Clinical Endocrinology and Metabolism |
| ISSN: | 1945-7197 |
| Popis: | Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Although the majority of childhood ACC arises in the context of inherited cancer susceptibility syndromes, it remains less clear whether a hereditary tumor predisposition exists for the development of ACC in adults. Here, we report the first occurrence of familial ACC in a kindred with Lynch syndrome resulting from a pathogenic germline MSH2 mutation. Case: A 54-year-old female with a history of ovarian and colorectal malignancy was found to have an ACC. A detailed family history revealed her mother had died of ACC and her sister had previously been diagnosed with endometrial and colorectal cancers. A unifying diagnosis of Lynch syndrome was considered, and immunohistochemical analyses demonstrated loss of MSH2 and MSH6 expression in both AACs (proband and her mother) and in the endometrial carcinoma of her sister. Subsequent genetic screening confirmed the presence of a germline MSH2 mutation (resulting in deletions of exons 1–3) in the proband and her sister. Conclusion: Our findings provide strong support for the recent proposal that ACC should be considered a Lynch syndrome-associated tumor and included in the Amsterdam II clinical diagnostic criteria. We also suggest that screening for ACC should be considered in cancer surveillance strategies directed at individuals with germline mutations in DNA mismatch repair genes. This study provides the first description of an intergenerational occurrence of ACC in a family with Lynch Syndrome resulting from a germline MSH2 mutation. Thus, ACC should be included in clinical diagnostic criteria for LS and considered in cancer surveillance recommendations for individuals with germline mutations in DNA mismatch repair genes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|