Shared and unique genomic structural variants of different histological components within testicular germ cell tumours identified with mate pair sequencing

Alan H Bryce, Jan B. Egan, James Smadbeck, Sarah H. Johnson, Stephen J. Murphy, Faye R. Harris, Geoffrey C. Halling, Simone B.S.P. Terra, John Cheville, Lance Pagliaro, Bradley Leibovich, Brian Costello, George Vasmatzis

Research output: Contribution to journalArticle

Abstract

Post-pubertal testicular germ-cell tumours (TGCTs) can present with a variety of distinct histologies which are nevertheless lineage related and often co-occurring. The exact lineage relationships and developmental pathways leading to the different histologies is debated. In order to investigate the relationship of histologic populations, mate-pair sequencing (MPseq) and exome sequencing (ExomeSeq) were conducted on different histological populations within the same tumour. Ten TGCTs with 1–3 histologic types/tumour were sequenced. Junctions of somatic chromosomal rearrangements were identified on a per genome basis, with germ cell neoplasia in situ possessing the least (median 1, range 0–4) and embryonal carcinoma the most (median 8.5, range 6–12). Copy number variation revealed gains and losses, including isoform 12p (i12p) (10/10 samples), and chromosomes 7, 8, and 21 gains (7/10 samples). Mapping of shared junctions within a tumour revealed lineage relationships, but only i12p was shared between patients. ExomeSeq from two cases demonstrated a high level of copy-neutral loss of heterozygosity. Parallel assessment of separate histologies within a single TGCT demonstrated cumulative and divergent changes, suggesting the importance of parallel sequencing for detection of relevant biomarkers.

Original languageEnglish (US)
Article number3586
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Genomic Structural Variation
Exome
Histology
Neoplasms
Protein Isoforms
Embryonal Carcinoma
Chromosomes, Human, Pair 21
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 7
Loss of Heterozygosity
Germ Cells
Population
Biomarkers
Genome
Testicular Germ Cell Tumor

ASJC Scopus subject areas

  • General

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Shared and unique genomic structural variants of different histological components within testicular germ cell tumours identified with mate pair sequencing. / Bryce, Alan H; Egan, Jan B.; Smadbeck, James; Johnson, Sarah H.; Murphy, Stephen J.; Harris, Faye R.; Halling, Geoffrey C.; Terra, Simone B.S.P.; Cheville, John; Pagliaro, Lance; Leibovich, Bradley; Costello, Brian; Vasmatzis, George.

In: Scientific reports, Vol. 9, No. 1, 3586, 01.12.2019.

Research output: Contribution to journalArticle

Bryce, Alan H ; Egan, Jan B. ; Smadbeck, James ; Johnson, Sarah H. ; Murphy, Stephen J. ; Harris, Faye R. ; Halling, Geoffrey C. ; Terra, Simone B.S.P. ; Cheville, John ; Pagliaro, Lance ; Leibovich, Bradley ; Costello, Brian ; Vasmatzis, George. / Shared and unique genomic structural variants of different histological components within testicular germ cell tumours identified with mate pair sequencing. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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