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.

TitleAcquired 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.
Publication TypeJournal Article
Year of Publication2014
AuthorsOshrine BR, Olsen MN, Heneghan M, Wertheim G, Daber R, Wilmoth DM, Biegel JA, Pawel B, Aplenc R, King RL
JournalCancer Genet
Volume207
Issue4
Pagination153-9
Date Published2014 Apr
ISSN2210-7762
KeywordsAdolescent, Chromosomes, Human, Pair 12, Germ-Line Mutation, Humans, In Situ Hybridization, Fluorescence, Isochromosomes, Karyotyping, Leukemia, Megakaryoblastic, Acute, Male, Mutation, Neoplasms, Germ Cell and Embryonal, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, PTEN Phosphohydrolase, Testicular Neoplasms, Tumor Suppressor Protein p53
Abstract

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.

DOI10.1016/j.cancergen.2014.03.009
Alternate JournalCancer Genet
PubMed ID24831771