Acquired isochromosome 12p, somatic TP53 and PTEN mutations, and a germline ATM variant in an adolescent male with concurrent acute megakaryoblastic leukemia and mediastinal germ cell tumor

作者：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

来源：Cancer Genetics, 2014, 207(4): 153-159.

DOI：10.1016/j.cancergen.2014.03.009

• Germ cell tumor
• acute megakaryoblastic leukemia
• isochromosome 12p
• TP53
• PTEN
• ATM

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 OCT. 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 OCT 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 OCT or AMKL, suggesting that these tumors may represent unique biologic entities when they co-occur.

• 出版日期2014-4