In vivo differentiation and genomic evolution in adult male germ cell tumors Journal Article


Authors: Korkola, J. E.; Heck, S.; Olshen, A. B.; Reuter, V. E.; Bosl, G. J.; Houldsworth, J.; Chaganti, R. S. K.
Article Title: In vivo differentiation and genomic evolution in adult male germ cell tumors
Abstract: Germ cell tumors (GCTs) are the most common solid malignancy in young adult men, but the genes and genomic regions involved in their etiology are not fully defined. We report here an investigation of DNA copy number changes in GCTs using 1 Mb BAC arrays. As expected, 12p gain was the defining genomic alteration, occurring in 72/74 GCTs. Parallel expression profiling of these tumors identified potential oncogenes from gained regions (LYN and RAB25) and potential tumor suppressor genes in regions of loss (SYNPO2, TTC12, IGSF4, and EPB41L3). Notably, we observed specific genomic alterations associated with histology, including gain of 17p1l.2-q21.32 and loss of 2p25.3 in embryonal carcinoma, gain of 8p23.3-12 and loss of 5p15.33-35.3, 11q23.1-25, and 13q12.11-34 in seminoma, and gain of 1q31.3-42.3, 3p, 14q11.2-32.33, and 20q and loss of 8q11.1-23.1 in yolk sac tumors (YST). Many significant genes that mapped to these regions had previously been associated with specific histologies, such as EOMES (chr3) and BMP2 (chr20) in YST and SPRY2 (chr13) and SOX17 (chr8) in seminomas. Additionally, our results suggest a model in which histologic differentiation of GCTs may drive genomic evolution. © 2007 Wiley-Liss, Inc.
Keywords: adult; controlled study; human tissue; gene mutation; major clinical study; tumor localization; gene expression profiling; analytic method; cell differentiation; histology; chromosomes, artificial, bacterial; evolution, molecular; oncogene; tumor suppressor gene; oligonucleotide array sequence analysis; testicular neoplasms; genomics; gene dosage; nucleic acid hybridization; germ cell tumor; chromosome loss; embryonal carcinoma; chromosome 11q; genome, human; chromosome 5p; chromosome 17p; chromosome 13q; germinoma; chromosome 2p
Journal Title: Genes Chromosomes and Cancer
Volume: 47
Issue: 1
ISSN: 1045-2257
Publisher: Wiley Periodicals, Inc  
Date Published: 2008-01-01
Start Page: 43
End Page: 55
Language: English
DOI: 10.1002/gcc.20504
PUBMED: 17943972
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 22" - "Export Date: 17 November 2011" - "CODEN: GCCAE" - "Source: Scopus"
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MSK Authors
  1. James E Korkola
    24 Korkola
  2. Adam B Olshen
    107 Olshen
  3. Victor Reuter
    1227 Reuter
  4. Raju S K Chaganti
    391 Chaganti
  5. George Bosl
    430 Bosl