Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers

Paula M. Hempen, Lin Zhang, Ravi K. Bansal, Christine A. Iacobuzio-Donahue, Kathleen M. Murphy, Anirban Maitra, Bert Vogelstein, Robert H. Whitehead, Sanford D. Markowitz, James K V Willson, Charles J. Yeo, Ralph H. Hruban, Scott E. Kern

Research output: Contribution to journalArticle

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Abstract

The activin signaling pathway parallels the transforming growth factor (TGF)-β pathway. Both use extracellular ligands and cell surface receptors that are structurally and functionally related, as well as the same intracellular mediators (SMADs 2-4) to transmit these signals. Members of both pathways have been characterized previously as tumor suppressor genes on the demonstration of inactivating mutations in human neoplasms, e.g., genetic inactivation of the activin type I receptor was reported recently in pancreatic cancer. Here, we present evidence of selection for mutations of the activin A type II receptor (ACVR2) gene during human gastrointestinal carcinogenesis. Two 8-bp polyadenine tracts of the ACVR2 gene are targets for inactivating frameshift mutations in gastrointestinal neoplasms having microsatellite instability (MSI). These mutations are similar to those of the 10-bp polyadenine tract within the TGF-β type II receptor (TGFBR2), a well-characterized target of frameshift mutations in the same neoplasms. We identified biallelic mutations of ACVR2 in 25 of 28 MSI colorectal and pancreatic cancers. In addition, a mutation in the ACVR2 gene combined with loss of the wild-type allele was found in a non-MSI pancreatic cancer. This evidence is compatible with a high degree of selection for inactivation of the ACVR2 gene in tumorigenesis, supporting ACVR2 as a candidate tumor suppressor gene in gastrointestinal cancers.

Original languageEnglish (US)
Pages (from-to)994-999
Number of pages6
JournalCancer Research
Volume63
Issue number5
StatePublished - Mar 1 2003

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Gastrointestinal Neoplasms
Clone Cells
Mutation
Pancreatic Neoplasms
Microsatellite Instability
Frameshift Mutation
Genes
Transforming Growth Factors
Tumor Suppressor Genes
Type I Activin Receptors
Carcinogenesis
Activins
Growth Factor Receptors
Cell Surface Receptors
Gene Silencing
Colorectal Neoplasms
Neoplasms
Alleles
activin receptor type II-A
Ligands

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hempen, P. M., Zhang, L., Bansal, R. K., Iacobuzio-Donahue, C. A., Murphy, K. M., Maitra, A., ... Kern, S. E. (2003). Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers. Cancer Research, 63(5), 994-999.

Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers. / Hempen, Paula M.; Zhang, Lin; Bansal, Ravi K.; Iacobuzio-Donahue, Christine A.; Murphy, Kathleen M.; Maitra, Anirban; Vogelstein, Bert; Whitehead, Robert H.; Markowitz, Sanford D.; Willson, James K V; Yeo, Charles J.; Hruban, Ralph H.; Kern, Scott E.

In: Cancer Research, Vol. 63, No. 5, 01.03.2003, p. 994-999.

Research output: Contribution to journalArticle

Hempen, PM, Zhang, L, Bansal, RK, Iacobuzio-Donahue, CA, Murphy, KM, Maitra, A, Vogelstein, B, Whitehead, RH, Markowitz, SD, Willson, JKV, Yeo, CJ, Hruban, RH & Kern, SE 2003, 'Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers', Cancer Research, vol. 63, no. 5, pp. 994-999.
Hempen PM, Zhang L, Bansal RK, Iacobuzio-Donahue CA, Murphy KM, Maitra A et al. Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers. Cancer Research. 2003 Mar 1;63(5):994-999.
Hempen, Paula M. ; Zhang, Lin ; Bansal, Ravi K. ; Iacobuzio-Donahue, Christine A. ; Murphy, Kathleen M. ; Maitra, Anirban ; Vogelstein, Bert ; Whitehead, Robert H. ; Markowitz, Sanford D. ; Willson, James K V ; Yeo, Charles J. ; Hruban, Ralph H. ; Kern, Scott E. / Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers. In: Cancer Research. 2003 ; Vol. 63, No. 5. pp. 994-999.
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