Oshrine Benjamin R, Olsen Molly N, Heneghan Mallorie, Wertheim Gerald, Daber Robert, Wilmoth Donna M, Biegel Jaclyn A, Pawel Bruce, Aplenc Richard, King Rebecca L
Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cancer Genet. 2014 Apr;207(4):153-9. doi: 10.1016/j.cancergen.2014.03.009. Epub 2014 Apr 5.
Previous reports have described an association between hematologic malignancies (HMs) and extragonadal germ cell tumor (GCT). Most patients have been adolescent males with mediastinal nonseminomatous GCT. Although a variety of HMs have been reported, there is a striking predilection toward acute megakaryoblastic leukemia (AMKL). Shared cytogenetic anomalies--particularly isochromosome 12p [i(12p)]--have suggested common clonal origins to the tumors. We report the case of a 17-year-old boy presenting with AMKL and a synchronous mediastinal GCT, with the characteristic i(12p) in both neoplasms. The common clonal origin of the AMKL and GCT was further confirmed with massively parallel sequencing, which identified somatic TP53 and PTEN mutations, as well as a rare germline ATM variant. Although these represent commonly mutated genes in cancer, this combination of mutations is not typically associated with either GCT or AMKL, suggesting that these tumors may represent unique biologic entities when they co-occur.
既往报道描述了血液系统恶性肿瘤（HMs）与性腺外生殖细胞肿瘤（GCT）之间的关联。大多数患者为患有纵隔非精原细胞瘤性GCT的青少年男性。尽管已报道了多种HMs，但急性巨核细胞白血病（AMKL）有明显的偏好。共同的细胞遗传学异常——特别是12号染色体等臂染色体[i(12p)]——提示肿瘤有共同的克隆起源。我们报告了一例17岁男孩，患有AMKL并同时患有纵隔GCT，两种肿瘤均有特征性的i(12p)。通过大规模平行测序进一步证实了AMKL和GCT的共同克隆起源，该测序鉴定出体细胞TP53和PTEN突变，以及一种罕见的胚系ATM变异。虽然这些代表了癌症中常见的突变基因，但这种突变组合通常与GCT或AMKL均无关联，这表明这些肿瘤同时出现时可能代表独特的生物学实体。
