Brain Metastases: Gene Amplification Using Quantitative Real-Time Polymerase Chain Reaction Analysis

  • Carmen Franco-Hernandez
  • Miguel Torres-Martin
  • Victor Martinez-Glez
  • Carolina Peña-Granero
  • Javier S. Castresana
  • Cacilda Casartelli
  • Juan A. Rey
Chapter
First Online:
Part of the Methods of Cancer Diagnosis, Therapy and Prognosis book series (HAYAT, volume 8)

Abstract

Brain metastasis is the most common intracranial malignancy in adults, occurring in about 10 to 30% of adult cancer patients. Tumor metastasis is a complex process requiring cell motility, invasion, platelet aggregation ability, angiogenesis, and avoidance of host immune responses. Increasing gene dosage through oncogene copy gain (extra copies) or amplification is a common genetic mechanism for up-regulation of gene expression; this mechanism participates in the development of solid tumors and metastases by stimulation of cell division or by inhibition of cell death or cell cycle arrest. Using quantitative real time polymerase chain reaction we determined gene dosage of eight tumor-related genes: ELF3, MDM4, LRRN2, PDGFRA, EGFR, MYC, MDM2, and ERBB2, in a series of 18 brain metastases originated from lung cancer (six cases), breast carcinoma (three cases), melanoma (three samples), ovarian carcinoma (two cases), and one each from colon, bladder, kidney and undifferentiated carcinoma. Copy gains, in at least one gene, were identified in ten cases (55%) whereas amplification could be determined in six samples (33%). Concurrent alterations were observed in three lesions derived from two lung carcinoma and from one ovarian carcinoma: one of the lung carcinoma metastases accumulated copy gains of LRRN2, MDM2, PDGFRA, and ERBB2, whereas the second displayed amplification of LRNN2 and ERBB2. The lesion derived from the ovarian carcinoma accumulated amplification of MYC and EGFR. Differential amplification levels could be determined for the intracellular / extracellular domains of genes EGFR and/or ERBB2 in four cases. These data suggest that copy gain/gene amplification appears associated with greater tumor aggressiveness and that quantitative real time polymerase chain reaction is an alternative methodology to identify differential intragenic amplification levels.

Keywords

Brain Metastasis Ovarian Carcinoma Gene Dosage Viral Oncogene Homolog Copy Gain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Netherlands 2011

Authors and Affiliations

  • Carmen Franco-Hernandez
    • 1
  • Miguel Torres-Martin
    • 1
  • Victor Martinez-Glez
    • 1
  • Carolina Peña-Granero
    • 1
  • Javier S. Castresana
    • 1
  • Cacilda Casartelli
    • 1
  • Juan A. Rey
    • 1
  1. 1.Unidad de InvestigacionHospital Universitario La PazMadridSpain

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