Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States; Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, United States.
Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States; Department of Surgery, Rutgers Robert Wood Johnson University School of Medicine, New Brunswick, NJ 08901, United States.
Cancer Genet. 2021 Aug;256-257:21-25. doi: 10.1016/j.cancergen.2021.03.003. Epub 2021 Mar 24.
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.
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.
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.
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.
肾上腺皮质癌（ACC）是一种罕见的起源于肾上腺皮质的恶性肿瘤。ACC 的预后较差，手术是治愈的唯一机会。某些癌基因中的种系致病性变异与 ACC 有关。在这里，我们报告了首例 ATM 基因种系致病性变异患者的 ACC 病例。
一名 56 岁白人女性，经活检证实为不可切除的 ACC，接受依托泊苷、多柔比星和顺铂（EDP）和米托坦治疗，因评估就诊于我院。肿瘤标本进行了病理检查，并对肿瘤和种系使用下一代测序进行了基因分析。
病理评估显示，肿瘤无残留切缘的低级别 ACC，大小为 18.0×14.0×9.0cm。免疫组化染色显示抑制素、黑色素-A 和嗜铬粒蛋白阳性。ClinOmics 分析显示，ATM 的一个核苷酸的种系致病性缺失突变，在 cDNA 水平表示为 c.1215delT，在蛋白质水平表示为 p.Asn405LysfsX15（N405KfsX15）。肿瘤的基因组分析显示，ATM 所在的 11 号染色体存在杂合性丢失（LOH）。
ACC 是一种侵袭性恶性肿瘤，目前手术切除是唯一的治愈选择。在这里，我们报告了一名 ACC 患者的种系 DNA 中存在杂合失活突变和肿瘤中 ATM 的 LOH，这是一种在著名的肿瘤抑制基因中常见的“两次打击”情况，提示 ATM 基因在某些 ACC 病例中起致病作用。
