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.
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.
Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: oshrineb@email.chop.edu.
Benjamin R
BR
Oshrine
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Molly N
MN
Olsen
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mallorie
M
Heneghan
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Gerald
G
Wertheim
Department of Pathology and Lab Medicine, Center for Personalized Diagnostics, University of Pennsylvania, Philadelphia, PA, USA.
Robert
R
Daber
Department of Pathology and Lab Medicine, Center for Personalized Diagnostics, University of Pennsylvania, Philadelphia, PA, USA.
Donna M
DM
Wilmoth
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Jaclyn A
JA
Biegel
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Bruce
B
Pawel
Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Richard
R
Aplenc
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Rebecca L
RL
King
D000293:Adolescent; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018404:Isochromosomes; D007621:Karyotyping; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics*; D008297:Male; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013736:Testicular Neoplasms; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
ATM; Germ cell tumor; PTEN; TP53; acute megakaryoblastic leukemia; isochromosome 12p