Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages

Neoplasia : an International Journal for Oncology Research
Sigmund BrabrandRolf I Skotheim

Abstract

Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes su...Continue Reading

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Citations

Jan 20, 2016·Molecular and Cellular Neurosciences·Francesca RizzoAlessandro Weisz
Mar 15, 2019·PloS One·Michael T BarrettAlan H Bryce
Feb 12, 2019·British Journal of Cancer·Lambert C J DorssersLeendert H J Looijenga
Dec 15, 2015·Cancer Research·Andreas M HoffRolf I Skotheim

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Methods Mentioned

BETA
exome sequencing
PCR
electrophoresis
exome-sequencing

Software Mentioned

HaplotypeCaller
IndelRealigner
Mutation Assessor
Burrows
GATK
FixMateInformation
SomaticIndelDetector
Picard
ANNOVAR
RealignerTargetCreator

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