Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages

• DOI: 10.1016/j.neo.2014.12.005
• Publication Date: 2015-03-03T22:03:01Z
• Authors: Sigmund Brabrand; Bjarne Johannessen; Ulrika Axcrona; Sigrid M. Kraggerud; Kaja G. Berg; Anne C. Bakken; Jarle Bruun; Sophie D. Fosså; Ragnhild A. Lothe; Gustav Lehne; Rolf I. Skotheim
• Keywords: Exome; PDGFRA; Sanger sequencing; Malignant Transformation

Intratubular germ cell neoplasia, the precursor of testicular tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial cells (PGCs) or gonocytes.In early embryonal life, PGCs migrate yolk sac dorsal body wall where population separates before colonizing genital ridges.However, whether malignant transformation takes place after this separation controversial.We have explored somatic exome-wide mutational spectra bilateral TGCT provide novel insight into in utero critical time frame and pathogenesis.Exome sequencing was performed five patients with (eight tumors), these three whom both were available (six tumors) two each only one tumor (two tumors).Selected loci by Sanger 71 TGCT.From spectra, no identical mutations any pairs identified.Exome all eight revealed 87 non-synonymous (median 10 per tumor; range 5-21), some already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), WHSC1.SUPT6H found recurrently mutated tumors.We suggest independent development lineages TGCT.Thus, intratubular neoplasia likely occur migration PGCs.We reveal possible drivers pathogenesis, PDGFRA, potentially therapeutic implications for patients.