Clonal analyses of refractory testicular germ cell tumors

Michael Barrett, Elzbieta Lenkiewicz, Smriti Malasi, Melissa Stanton, James L Slack, Paul Andrews, Lance Pagliaro, Alan H Bryce

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Testicular germ cell tumors (TGCTs) are unique amongst solid tumors in terms of the high cure rates using chemotherapy for metastatic disease. Nevertheless, TGCTs still kill approximately 400 men per year, at a median age of 30 years, in the United States. This young age of mortality dramatically amplifies the impact of these deaths for the patients and their often young families. Furthermore the high cure rate makes it difficult to conduct further clinical trials of non curable disease. TGCTs are characterized by a marked aneuploidy and the presence of gain of chromosomal region 12p. Genomic testing may offer the ability to identify potentially lethal TGCTs at the time of initial diagnosis. However sequencing based studies have shown a paucity of somatic mutations in TGCT genomes including those that drive refractory disease. Furthermore these studies may be limited by genetic heterogeneity in primary tumors and the evolution of sub populations during disease progression. Herein we applied a systematic approach combining DNA content flow cytometry, whole genome copy number and whole exome sequence analyses to interrogate tumor heterogeneity in primary and metastatic refractory TGCTs. We identified both known and novel somatic copy number aberrations (12p, MDM2, and RHBDD1) and mutations (XRCC2, PIK3CA, RITA1) including candidate markers for platinum resistance that were present in a primary tumor of mixed histology and that remained after tandem autologous stem cell transplant.

Original languageEnglish (US)
Article numbere0213815
JournalPloS one
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Refractory materials
Tumors
germ cells
Cells
neoplasms
Neoplasms
Genome
Exome
Mutation
Aptitude
Genetic Heterogeneity
Aneuploidy
Platinum
Genes
Sequence Analysis
Disease Progression
Testicular Germ Cell Tumor
Histology
Flow Cytometry
Stem Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Clonal analyses of refractory testicular germ cell tumors. / Barrett, Michael; Lenkiewicz, Elzbieta; Malasi, Smriti; Stanton, Melissa; Slack, James L; Andrews, Paul; Pagliaro, Lance; Bryce, Alan H.

In: PloS one, Vol. 14, No. 3, e0213815, 01.03.2019.

Research output: Contribution to journalArticle

Barrett, M, Lenkiewicz, E, Malasi, S, Stanton, M, Slack, JL, Andrews, P, Pagliaro, L & Bryce, AH 2019, 'Clonal analyses of refractory testicular germ cell tumors', PloS one, vol. 14, no. 3, e0213815. https://doi.org/10.1371/journal.pone.0213815
Barrett M, Lenkiewicz E, Malasi S, Stanton M, Slack JL, Andrews P et al. Clonal analyses of refractory testicular germ cell tumors. PloS one. 2019 Mar 1;14(3). e0213815. https://doi.org/10.1371/journal.pone.0213815
Barrett, Michael ; Lenkiewicz, Elzbieta ; Malasi, Smriti ; Stanton, Melissa ; Slack, James L ; Andrews, Paul ; Pagliaro, Lance ; Bryce, Alan H. / Clonal analyses of refractory testicular germ cell tumors. In: PloS one. 2019 ; Vol. 14, No. 3.
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