Frequent loss of heterozygosity at chromosome 3p14.2-3p21 in human pancreatic islet cell tumours

Marina N. Nikiforova, Yuri E. Nikiforov, Paul Williams Biddinger, Douglas R. Gnepp, Luis A. Grosembacher, Bernardo L. Wajchenberg, James A. Fagin, Robert M. Cohen

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

OBJECTIVE: Pancreatic islet βcell tumours occur either sporadically or as part of inherited neoplastic syndromes, most commonly multiple endocrine neoplasia (MEN) type 1. Recently, a transgenic mouse model has been established in which the expression of the SV40 large T antigen was targeted to βcells by the rat insulin promoter, leading to the development of multiple pancreatic βcell tumours. In the advanced stages of tumour evolution, these tumours exhibited a high prevalence of loss of heterozygosity (LOH) on mouse chromosomes 9 and 16, at regions syntenic with regions 3q, 3p21, 6q12, 15q24 and 22q of the human genome. DESIGN: Loss of heterozygosity in human islet cell tumours was analysed in a PCR based approach at regions of the human genome syntenic with the mouse loci linked to pancreatic βcell tumours as well as the MEN1 gene on chromosome 11q13. These included 35 microsatellite markers in the human chromosomal regions 3q, 3p21, 6q12, 11q13, 15q24 and 22q. PATIENTS: 21 patients diagnosed with insulinoma were analysed. Histologically, 16 tumours were benign, while 5 were malignant insulinomas. RESULTS: Thirteen of 21 (62%) tumours were found to have loss of genetic material on chromosome 3. The shortest region of overlap implicated a deletion at 3p14.2-3p21 region, corresponding to the marker D3S1295. We did not detect a substantial frequency of LOH in the other syntenic regions, except for the region of MEN 1 gene on 11q13 found to be deleted in 6 (29%) cases, including 3 of 4 tumours from MEN 1 families. Deletions of 3p14.2-3p21 were observed in 8 of 15 (53%) benign tumours, and in 5 of 6 (83%) malignant neoplasms. CONCLUSIONS: These results indicate the high frequency of 3p14.2-3p21 deletions in human pancreatic βcell neoplasms. These finding suggest the presence of a tumour suppressor gene in this region, that may be important in the microevolution of these tumours towards malignancy.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalClinical Endocrinology
Volume51
Issue number1
DOIs
StatePublished - Jul 29 1999
Externally publishedYes

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Loss of Heterozygosity
Chromosomes
Neoplasms
Multiple Endocrine Neoplasia
Multiple Endocrine Neoplasia Type 1
Insulinoma
Human Genome
Pancreatic islet cell tumors
Islet Cell Adenoma
Genes
Polyomavirus Transforming Antigens
Chromosomes, Human, Pair 16
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 3
Viral Tumor Antigens
Tumor Suppressor Genes
Pancreatic Neoplasms
Microsatellite Repeats
Transgenic Mice
Insulin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Nikiforova, M. N., Nikiforov, Y. E., Biddinger, P. W., Gnepp, D. R., Grosembacher, L. A., Wajchenberg, B. L., ... Cohen, R. M. (1999). Frequent loss of heterozygosity at chromosome 3p14.2-3p21 in human pancreatic islet cell tumours. Clinical Endocrinology, 51(1), 27-33. https://doi.org/10.1046/j.1365-2265.1999.00785.x

Frequent loss of heterozygosity at chromosome 3p14.2-3p21 in human pancreatic islet cell tumours. / Nikiforova, Marina N.; Nikiforov, Yuri E.; Biddinger, Paul Williams; Gnepp, Douglas R.; Grosembacher, Luis A.; Wajchenberg, Bernardo L.; Fagin, James A.; Cohen, Robert M.

In: Clinical Endocrinology, Vol. 51, No. 1, 29.07.1999, p. 27-33.

Research output: Contribution to journalArticle

Nikiforova, MN, Nikiforov, YE, Biddinger, PW, Gnepp, DR, Grosembacher, LA, Wajchenberg, BL, Fagin, JA & Cohen, RM 1999, 'Frequent loss of heterozygosity at chromosome 3p14.2-3p21 in human pancreatic islet cell tumours', Clinical Endocrinology, vol. 51, no. 1, pp. 27-33. https://doi.org/10.1046/j.1365-2265.1999.00785.x
Nikiforova, Marina N. ; Nikiforov, Yuri E. ; Biddinger, Paul Williams ; Gnepp, Douglas R. ; Grosembacher, Luis A. ; Wajchenberg, Bernardo L. ; Fagin, James A. ; Cohen, Robert M. / Frequent loss of heterozygosity at chromosome 3p14.2-3p21 in human pancreatic islet cell tumours. In: Clinical Endocrinology. 1999 ; Vol. 51, No. 1. pp. 27-33.
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AU - Nikiforov, Yuri E.

AU - Biddinger, Paul Williams

AU - Gnepp, Douglas R.

AU - Grosembacher, Luis A.

AU - Wajchenberg, Bernardo L.

AU - Fagin, James A.

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