Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene

B. Mark Evers, Peter L. Rady, Ken Sandoval, Istvan Arany, Stephen K. Tyring, Ramon L. Sanchez, William H. Nealon, Courtney Townsend, James C. Thompson

Research output: Contribution to journalArticle

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Abstract

Objective: This study determined whether genomic amplification of HER- 2/neu or mutations of the p53 and ras genes were present in gastrinomas. Summary Background Data: Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto- oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. Methods: The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. Results: Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. Conclusions: Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.

Original languageEnglish (US)
Pages (from-to)596-604
Number of pages9
JournalAnnals of Surgery
Volume219
Issue number6
StatePublished - Jun 1994

Fingerprint

Gastrinoma
Proto-Oncogenes
erbB-2 Genes
ras Genes
Mutation
p53 Genes
Neoplasms
Zollinger-Ellison Syndrome
Cell Line
Disease Susceptibility
Gastrins
Tumor Suppressor Genes
Ileum
Point Mutation
Epidermal Growth Factor Receptor
Codon
Paraffin
Ulcer
Pancreas

ASJC Scopus subject areas

  • Surgery

Cite this

Evers, B. M., Rady, P. L., Sandoval, K., Arany, I., Tyring, S. K., Sanchez, R. L., ... Thompson, J. C. (1994). Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene. Annals of Surgery, 219(6), 596-604.

Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene. / Evers, B. Mark; Rady, Peter L.; Sandoval, Ken; Arany, Istvan; Tyring, Stephen K.; Sanchez, Ramon L.; Nealon, William H.; Townsend, Courtney; Thompson, James C.

In: Annals of Surgery, Vol. 219, No. 6, 06.1994, p. 596-604.

Research output: Contribution to journalArticle

Evers, BM, Rady, PL, Sandoval, K, Arany, I, Tyring, SK, Sanchez, RL, Nealon, WH, Townsend, C & Thompson, JC 1994, 'Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene', Annals of Surgery, vol. 219, no. 6, pp. 596-604.
Evers BM, Rady PL, Sandoval K, Arany I, Tyring SK, Sanchez RL et al. Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene. Annals of Surgery. 1994 Jun;219(6):596-604.
Evers, B. Mark ; Rady, Peter L. ; Sandoval, Ken ; Arany, Istvan ; Tyring, Stephen K. ; Sanchez, Ramon L. ; Nealon, William H. ; Townsend, Courtney ; Thompson, James C. / Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene. In: Annals of Surgery. 1994 ; Vol. 219, No. 6. pp. 596-604.
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abstract = "Objective: This study determined whether genomic amplification of HER- 2/neu or mutations of the p53 and ras genes were present in gastrinomas. Summary Background Data: Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto- oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. Methods: The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. Results: Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. Conclusions: Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.",
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AU - Evers, B. Mark

AU - Rady, Peter L.

AU - Sandoval, Ken

AU - Arany, Istvan

AU - Tyring, Stephen K.

AU - Sanchez, Ramon L.

AU - Nealon, William H.

AU - Townsend, Courtney

AU - Thompson, James C.

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N2 - Objective: This study determined whether genomic amplification of HER- 2/neu or mutations of the p53 and ras genes were present in gastrinomas. Summary Background Data: Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto- oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. Methods: The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. Results: Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. Conclusions: Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.

AB - Objective: This study determined whether genomic amplification of HER- 2/neu or mutations of the p53 and ras genes were present in gastrinomas. Summary Background Data: Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto- oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. Methods: The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. Results: Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. Conclusions: Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.

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