Article

Molecular Biology

, Volume 37, Issue 3, pp 404-411

First online:

Genetic Alterations at Chromosome 6 Associated with Cervical Cancer Progression

  • N. N. MazurenkoAffiliated withInstitute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences
  • , I. S. BeliakovAffiliated withInstitute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences
  • , A. Yu. BliyevAffiliated withInstitute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences
  • , Z. GuoAffiliated withDepartment of Genetics and Pathology, Uppsala University
  • , X. HuAffiliated withDepartment of Genetics and Pathology, Uppsala University
  • , S. V. VinokourovaAffiliated withInstitute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences
  • , B. A. BidzhievaAffiliated withInstitute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences
  • , L. S. PavlovaAffiliated withInstitute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences
  • , J. PontenAffiliated withDepartment of Genetics and Pathology, Uppsala University
    • , F. L. KisseljovAffiliated withInstitute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences

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Abstract

Loss of heterozygosity (LOH) analysis on chromosome 6 was performed to define the genetic changes that occur in the development of squamous cell cervical cancer (SCC). Detailed analysis with 28 microsatellite markers revealed several loci with high frequency of deletions at the short (6p25, 6p22, 6p21.3) and long (6q14, 6q16–q21, 6q23–q24, 6q25, 6q27) arms of chromosome 6. Examination of microdissected 37 SCC and 22 cervical intraepithelial neoplasias (CIN) revealed allelic deletions in the HLA class I–III region (6p22–p21.3) and at subtelomeric locus 6p25-ter in more than 40% of CIN. By a combination of LOH and microdissection of multiple samples from the same tumor sections, we studied the intratumoral genetic heterogeneity of SCC, and identified clonal and subclonal allelic deletions. Half of SCC had clonal allelic deletion at D6S273, which is localized in intron of Ly6G6D (MEGT1) gene mapped in the HLA class III region. The LOH frequency at 6q in CIN cases did not exceed 20%. Allelic deletions at two loci, 6q14 and 6q16–q21, were for the first time associated with invasion and metastasis in SCC.

chromosome 6 loss of heterozygosity squamous cervical carcinoma CIN clonality progression HLA genes