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Genetic alterations on 3p, 11q13, and 18q in nonfamilial and MEN 1-associated pancreatic endocrine tumors.
Genes Chromosomes Cancer. 1999 Nov; 26(3):258-64.GC

Abstract

Pancreatic endocrine tumors occur sporadically and as part of the multiple endocrine neoplasia type 1 (MEN 1) and von Hippel-Lindau (VHL) syndromes. The MEN1 locus on 11q13 and a candidate tumor suppressor locus on 3p are known to be hemi- or homozygously mutated in a subset of these tumors. Chromosome arm 18q harbors the SMAD4/DPC4 tumor suppressor gene that is frequently deleted and inactivated in tumors of the exocrine pancreas. We have analyzed 22 nonfamilial and 16 MEN 1-associated pancreatic endocrine tumors for loss of heterozygosity (LOH) at 3p, 11q13, and 18q. LOH at 3p was revealed in 45% and 36% of tumors from 31 patients with nonfamilial and MEN 1-associated disease, respectively. The corresponding proportions for 11q13 were 55% and 91%, and for 18q 27% and 25%, respectively. A striking relation between LOH at 11q13 and 3p and a malignant phenotype was found for the nonfamilial tumors. None of the six benign tumors (all of them insulinomas) had allelic loss at 3p or 11q13, whereas 92% (P < 0.01) of the malignant tumors (including malignant insulinomas) had such deletions. Besides the 11q13 abnormality, more than half of the MEN 1-associated tumors had additional genetic lesions affecting 3p or 18q. LOH analysis of several tumors from two MEN 1 patients suggested different clonal origin of the lesions. Sequencing of the SMAD4/DPC4 gene did not identify mutations in coding regions or at exon/intron boundaries in tumors with LOH at 18q. The data indicate involvement of tumor suppressor genes on 3p and 18q, in addition to the MEN1 gene at 11q13, in the tumorigenesis of both nonfamilial and MEN 1-associated pancreatic endocrine tumors.

Authors+Show Affiliations

Department of Surgery, Endocrine Unit, Uppsala University Hospital, Uppsala, Sweden. ola.hessman@kirugi.uu.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10502325

Citation

Hessman, O, et al. "Genetic Alterations On 3p, 11q13, and 18q in Nonfamilial and MEN 1-associated Pancreatic Endocrine Tumors." Genes, Chromosomes & Cancer, vol. 26, no. 3, 1999, pp. 258-64.
Hessman O, Lindberg D, Einarsson A, et al. Genetic alterations on 3p, 11q13, and 18q in nonfamilial and MEN 1-associated pancreatic endocrine tumors. Genes Chromosomes Cancer. 1999;26(3):258-64.
Hessman, O., Lindberg, D., Einarsson, A., Lillhager, P., Carling, T., Grimelius, L., Eriksson, B., Akerström, G., Westin, G., & Skogseid, B. (1999). Genetic alterations on 3p, 11q13, and 18q in nonfamilial and MEN 1-associated pancreatic endocrine tumors. Genes, Chromosomes & Cancer, 26(3), 258-64.
Hessman O, et al. Genetic Alterations On 3p, 11q13, and 18q in Nonfamilial and MEN 1-associated Pancreatic Endocrine Tumors. Genes Chromosomes Cancer. 1999;26(3):258-64. PubMed PMID: 10502325.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic alterations on 3p, 11q13, and 18q in nonfamilial and MEN 1-associated pancreatic endocrine tumors. AU - Hessman,O, AU - Lindberg,D, AU - Einarsson,A, AU - Lillhager,P, AU - Carling,T, AU - Grimelius,L, AU - Eriksson,B, AU - Akerström,G, AU - Westin,G, AU - Skogseid,B, PY - 1999/9/29/pubmed PY - 1999/9/29/medline PY - 1999/9/29/entrez SP - 258 EP - 64 JF - Genes, chromosomes & cancer JO - Genes Chromosomes Cancer VL - 26 IS - 3 N2 - Pancreatic endocrine tumors occur sporadically and as part of the multiple endocrine neoplasia type 1 (MEN 1) and von Hippel-Lindau (VHL) syndromes. The MEN1 locus on 11q13 and a candidate tumor suppressor locus on 3p are known to be hemi- or homozygously mutated in a subset of these tumors. Chromosome arm 18q harbors the SMAD4/DPC4 tumor suppressor gene that is frequently deleted and inactivated in tumors of the exocrine pancreas. We have analyzed 22 nonfamilial and 16 MEN 1-associated pancreatic endocrine tumors for loss of heterozygosity (LOH) at 3p, 11q13, and 18q. LOH at 3p was revealed in 45% and 36% of tumors from 31 patients with nonfamilial and MEN 1-associated disease, respectively. The corresponding proportions for 11q13 were 55% and 91%, and for 18q 27% and 25%, respectively. A striking relation between LOH at 11q13 and 3p and a malignant phenotype was found for the nonfamilial tumors. None of the six benign tumors (all of them insulinomas) had allelic loss at 3p or 11q13, whereas 92% (P < 0.01) of the malignant tumors (including malignant insulinomas) had such deletions. Besides the 11q13 abnormality, more than half of the MEN 1-associated tumors had additional genetic lesions affecting 3p or 18q. LOH analysis of several tumors from two MEN 1 patients suggested different clonal origin of the lesions. Sequencing of the SMAD4/DPC4 gene did not identify mutations in coding regions or at exon/intron boundaries in tumors with LOH at 18q. The data indicate involvement of tumor suppressor genes on 3p and 18q, in addition to the MEN1 gene at 11q13, in the tumorigenesis of both nonfamilial and MEN 1-associated pancreatic endocrine tumors. SN - 1045-2257 UR - https://www.unboundmedicine.com/medline/citation/10502325/Genetic_alterations_on_3p_11q13_and_18q_in_nonfamilial_and_MEN_1_associated_pancreatic_endocrine_tumors_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1045-2257&amp;date=1999&amp;volume=26&amp;issue=3&amp;spage=258 DB - PRIME DP - Unbound Medicine ER -