Structural alterations of transforming growth factor-β receptor genes in human cervical carcinoma

Taiping Chen, E. G E De Vries, H. Hollema, H. A. Yegen, V. F. Vellucci, Howard Strickler, A. Hildesheim, M. Reiss

Research output: Contribution to journalArticle

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Abstract

The development and progression of invasive uterine cervical carcinomas appear to be associated with the progressive loss of sensitivity to transforming growth factor-β (TGFβ)mediated cell cycle arrest. In order to identify possible molecular mechanisms responsible for TGFβ resistance, we screened the 7 exons of the type II (TβR-II) TGFβ receptor and the 9 exons of the type I (TβR-I) TGFβ receptor genes for mutations in 16 paraffin- embedded primary invasive cervical carcinoma specimens. In one of these carcinomas, we found a novel G→T transversion in exon 3 of TβR-II that introduces a premature stop codon (E142Stop) and presumably results in the synthesis of a truncated soluble exoreceptor. In one tumor, a silent A→C transversion mutation that may affect mRNA splicing was present in exon 6 of TβR-I. In addition, 7 of 16 cases were heterozygous for a G→A polymorphism in intron 7 of TβR-I. Finally, we identified a 9 base pair in-frame germline deletion in exon I of TβR-I resulting in loss of 3 of 9 sequential alanine residues at the N-terminus in 6 of 16 cases. Analysis of specimens from case- control studies indicated that carriers of this del(GGC)3 TβR-I variant allele may be at a increased risk for the development of cervical carcinoma (p=0.22). Furthermore, the response of cells expressing the variant receptor to TGFβ was diminished. Our results support the notion that diverse alterations in the TGFβ signaling pathway may play a role in the development of cervical cancer.

Original languageEnglish (US)
Pages (from-to)43-51
Number of pages9
JournalInternational Journal of Cancer
Volume82
Issue number1
DOIs
StatePublished - Jul 2 1999
Externally publishedYes

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Growth Factor Receptors
Transforming Growth Factors
Exons
Carcinoma
Genes
Mutation
Nonsense Codon
Cell Cycle Checkpoints
Base Pairing
Uterine Cervical Neoplasms
Alanine
Paraffin
Introns
Case-Control Studies
Alleles
Messenger RNA
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Structural alterations of transforming growth factor-β receptor genes in human cervical carcinoma. / Chen, Taiping; De Vries, E. G E; Hollema, H.; Yegen, H. A.; Vellucci, V. F.; Strickler, Howard; Hildesheim, A.; Reiss, M.

In: International Journal of Cancer, Vol. 82, No. 1, 02.07.1999, p. 43-51.

Research output: Contribution to journalArticle

Chen, Taiping ; De Vries, E. G E ; Hollema, H. ; Yegen, H. A. ; Vellucci, V. F. ; Strickler, Howard ; Hildesheim, A. ; Reiss, M. / Structural alterations of transforming growth factor-β receptor genes in human cervical carcinoma. In: International Journal of Cancer. 1999 ; Vol. 82, No. 1. pp. 43-51.
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