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A novel MECA3 region in human 3p21.3 harboring putative tumor suppressor genes and oncogenes

E Braga1, W Loginov, D Khodyrev

  • 1Russian State Genetics Center, Moscow 117545 Russia. ebraga@genetika.ru

Experimental Oncology
|March 23, 2011
PubMed
Abstract

Insights

Researchers identified a new region on chromosome 3p (MECA3) frequently altered in epithelial cancers like breast, kidney, lung, and ovarian. This region contains potential oncogenes and tumor suppressors, including GPX1 and RHOA, offering new insights into cancer development.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Chromosome arm 3p, particularly the 3p21 region, is frequently altered in over 30 types of epithelial malignancies.
  • These alterations occur in cancers responsible for a significant portion of cancer-related deaths, highlighting the region's importance.
  • Previous studies have identified several tumor suppressor genes within this critical chromosomal region.

Purpose of the Study:

  • To conduct a detailed analysis of chromosome 3p, with a focus on the 3p21 region.
  • To identify novel potential oncogenes and tumor suppressor genes involved in epithelial cancers.
  • To map frequently altered regions within 3p relevant to major cancer types.

Main Methods:

  • Allelotyping of 24 dense 3p microsatellite markers.
  • Analysis of 272 patient samples from four epithelial carcinomas: breast (BC), renal cell (RCC), non-small cell lung (NSCLC), and epithelial ovarian (EOC).
  • Identification of "hot spots" and genes implicated in cancer development.

Main Results:

  • A novel region, MECA3 (3p21.3), was localized between markers D3S2409 and D3S3667, frequently affected in BC, RCC, NSCLC, and EOC.
  • MECA3 encompasses genes involved in vital cellular functions and carcinogenesis, such as MST1, MSTR1/RON, GPX1, and RHOA.
  • Homozygous deletions of GPX1 were observed in RCC and BC, while amplifications of the putative oncogene RHOA were found in BC and RCC.

Conclusions:

  • Genes with oncogenic potential and putative tumor suppressor genes (TSG(s)) are located in close proximity within the MECA3 region.
  • Novel findings include the multiplication of RHOA, previously unreported.
  • Significant correlations between allelic alterations in AP20, MECA3, and LUCA regions and tumor progression were identified for specific subtypes like clear cell RCC and serous EOC.

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