uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Mutation of the Multiple Endocrine Neoplasia Type 1 gene in nonfamilial, malignant tumors of the endocrine pancreas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Show others and affiliations
1998 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 58, no 3, 377-379 p.Article in journal (Refereed) Published
Abstract [en]

Endocrine pancreatic tumors are rare neoplasms that occur sporadically or as part of a multiple endocrine neoplasia type 1 (MEN1) syndrome. Germ-line mutations of the MEN1 gene, located at 11q13, have been demonstrated in MEN1 kindreds, and loss of heterozygosity (LOH) on 11q13 together with somatic MEN1 mutations have been detected in 20% of nonfamilial parathyroid tumors. Here, we examine 11 non-MEN1 malignant tumors of the endocrine pancreas, 9 nonfunctioning tumors, and 2 glucagonomas. LOH of at least one informative locus on 11q13 was found in 70% of the tumors. Three tumors displayed somatic mutations of the MEN1 gene together with LOH on 11q13, whereas the corresponding germ-line DNA was normal. These findings support the hypothesis that MEN1 gene mutations contribute to the tumorigenesis of nonfamilial, malignant endocrine pancreatic tumors.

Place, publisher, year, edition, pages
1998. Vol. 58, no 3, 377-379 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95504PubMedID: 9458074OAI: oai:DiVA.org:uu-95504DiVA: diva2:169746
Available from: 2007-03-01 Created: 2007-03-01 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Molecular Genetic Studies of Sporadic and MEN1-Associated Endocrine Pancreatic Tumors
Open this publication in new window or tab >>Molecular Genetic Studies of Sporadic and MEN1-Associated Endocrine Pancreatic Tumors
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pancreatic endocrine tumors (PETs) may cause typical syndromes of hormone excess, or appear clinically non-functioning without hormonal symptoms. PETs occur sporadically, in association with the multiple endocrine neoplasia type 1 (MEN1) syndrome, or rarely the von Hippel-Lindau syndrome. Molecular genetic investigations may reveal pathways important for tumor development, and be of clinical use.

The aim of this thesis was to investigate regulation of different genes involved in cell proliferation, and relate findings to signs of malignancy in PETs.

The MEN1 gene on chromosome 11q13 was mutated in three out of eleven sporadic malignant PETs. Two nonsense mutations, causing truncation of the protein, and one missense mutation were found.

Relation of allelic loss at 11q13 and 3p25 to malignant behavior was observed in sporadic PETs. Allelic loss at 18q21 was found in a subset of sporadic and MEN1-associated PETs, and mutation analysis of Smad4 excluded a tumor suppressor gene function.

In PETs with allelic loss on chromosome 3p25, mutation analysis of WNT7A and HDAC11 excluded function as tumor suppressor genes.

Menin, encoded by the MEN1 gene, was reported to regulate expression of the cyclin-dependent kinase inhibitors CDKN2C/p18, CDKN1B/p27, and CDKN2B/p15 in mouse pancreatic islet tumor models. Here, the mRNA expression of these genes was not related to MEN1 gene mutations in human PETs.

Cyclin-dependent kinase 4 (CDK4) and the protooncogene c-Myc were found to be overexpressed regardless of MEN1 gene mutational status of the PETs. The CDK4 gene was neither amplified nor mutated. Targeting of CDK4 may present an alternative to traditional chemotherapy of PETs in the future.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 231
Keyword
Surgery, pancreatic endocrine tumor, MEN1, LOH, WNT7A, HDAC11, CDK4, CDKN2B/p15, CDKN1B/p27, CDKN2C/p18, c-Myc, Smad4, pyrosequencing, epigenetic, methylation, tumor suppressor, Kirurgi
Identifiers
urn:nbn:se:uu:diva-7595 (URN)978-91-554-6810-1 (ISBN)
Public defence
2007-03-23, Rosénsalen, Kvinnokliniken, Akademiska sjukhuset ing 95, Uppsala, 13:00
Opponent
Supervisors
Available from: 2007-03-01 Created: 2007-03-01Bibliographically approved

Open Access in DiVA

No full text

Other links

PubMedhttp://cancerres.aacrjournals.org/content/58/3/377

Authority records BETA

Skogseid, Britt

Search in DiVA

By author/editor
Skogseid, Britt
By organisation
Endocrine SurgeryDepartment of Surgical SciencesInternal Medicine
In the same journal
Cancer Research
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

pubmed
urn-nbn

Altmetric score

pubmed
urn-nbn
Total: 469 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf