Cancer genetics · 2021
Ataxia telangiectasia mutated germline pathogenic variant in adrenocortical carcinoma.
Клинический случайСтатьяResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод пока не подготовлен
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Torres Madeline B, Diggs Laurence P, Wei Jun S, Khan Javed, Miettinen Markku, Fasaye Grace-Ann, Gillespie Andy, Widemann Brigitte C, Kaplan Rosandra N, Davis Jeremy L, Hernandez Jonathan M, Rivero Jaydira Del
Аннотация
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy arising from the adrenal cortex. ACC carries a dismal prognosis and surgery offers the only chance for a cure. Germline pathogenic variants among certain oncogenes have been implicated in ACC. Here, we report the first case of ACC in a patient with a pathogenic variant in the Ataxia Telangiectasia Mutated (ATM) gene.
PATIENTS AND METHODS: A 56-year-old Caucasian woman with biopsy proven ACC deemed unresectable and treated with etoposide, doxorubicin and cisplatin (EDP), and mitotane presented to our institution for evaluation. The tumor specimen was examined pathologically, and genetic analyses were performed on the tumor and germline using next-generation sequencing.
RESULTS: Pathologic evaluation revealed an 18.0 × 14.0 × 9.0 cm low-grade ACC with tumor free resection margins. Immunohistochemistry stained for inhibin, melan-A, and chromogranin. ClinOmics analysis revealed a germline pathogenic deletion mutation of one nucleotide in ATM is denoted as c.1215delT at the cDNA level and p.Asn405LysfsX15 (N405KfsX15) at the protein level. Genomic analysis of the tumor showed loss of heterozygosity (LOH) of chromosome 11 on which the ATM resides.
CONCLUSION: ACC is an aggressive malignancy for which surgical resection currently offers the only curative option. Here we report a heterozygous loss-of-function mutation in germline DNA and LOH of ATM in tumor in an ACC patient, a classic two-hit scenario in a well-known cancer suppresser gene, suggesting a pathogenic role of the ATM gene in certain ACC cases.
PATIENTS AND METHODS: A 56-year-old Caucasian woman with biopsy proven ACC deemed unresectable and treated with etoposide, doxorubicin and cisplatin (EDP), and mitotane presented to our institution for evaluation. The tumor specimen was examined pathologically, and genetic analyses were performed on the tumor and germline using next-generation sequencing.
RESULTS: Pathologic evaluation revealed an 18.0 × 14.0 × 9.0 cm low-grade ACC with tumor free resection margins. Immunohistochemistry stained for inhibin, melan-A, and chromogranin. ClinOmics analysis revealed a germline pathogenic deletion mutation of one nucleotide in ATM is denoted as c.1215delT at the cDNA level and p.Asn405LysfsX15 (N405KfsX15) at the protein level. Genomic analysis of the tumor showed loss of heterozygosity (LOH) of chromosome 11 on which the ATM resides.
CONCLUSION: ACC is an aggressive malignancy for which surgical resection currently offers the only curative option. Here we report a heterozygous loss-of-function mutation in germline DNA and LOH of ATM in tumor in an ACC patient, a classic two-hit scenario in a well-known cancer suppresser gene, suggesting a pathogenic role of the ATM gene in certain ACC cases.