Deletion mapping of endocrine tumors localizes a second tumor suppressor gene on chromosome band 11q13

Chakrabarti, Rita; Srivatsan, Eri S.; Wood, Tabitha E.; Eubanks, Patricia J.; Ebrahimi, Sam A.; Gatti, Richard A.; Passaro, Edward; Sawicki, Mark

doi:10.1002/(sici)1098-2264(199806)22:2<130::aid-gcc7>3.0.co;2-y

Cited by 69 publications

(50 citation statements)

References 28 publications

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“…2 Although approximately 50% of sporadic EPTs show allelic deletions of the MEN1 gene, the mutation rate was 2 to 3 times lower in frequency, pointing to the existence of yet another TSG more telo-meric of the MEN1 gene. 5,21,22 Consistent with this hypothesis, we found losses of 11q in 36% of EPTs, with the smallest CRI at 11q13-q22. In addition, we found losses of 11p (CRI: 11p13-p14) in 30% of cases, which is in accordance with other data 10 and might point to the Wilms' tumor gene WT1 on 11p13 as a potential candidate TSG.…”

Section: Discussionsupporting

confidence: 55%

Genetic Differences in Endocrine Pancreatic Tumor Subtypes Detected by Comparative Genomic Hybridization

Speel¹,

Richter²,

Moch³

et al. 1999

The American Journal of Pathology

144

122

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The molecular pathogenesis as well as histogenesis of endocrine pancreatic tumors (EPTs) is not well understood , and the clinical behavior of EPTs is difficult to predict using current morphological criteria. Thus, more accurate markers of risk and better understanding of tumor initiation and progression are needed to allow a precise classification of EPTs. We have studied 44 benign and malignant EPTs by comparative genomic hybridization to correlate the overall number of genetic alterations with clinical and histopathological parameters and to identify chromosomal regions which might harbor genes involved in EPT pathogenesis and progression. Aberrations were found in 36 EPTs , and chromosomal losses (mean, 5.3) were slightly more frequent than gains (mean, 4.6). The most frequent losses involved Y (45% of male EPTs) , 6q (39%) , 11q (36%) , 3p , 3q , 11p (each 30%) , 6p (27%) , and 10q and Xq (each 25%) , whereas most common gains included 7q (43%) , 17q (41%), 5q and 14q (each 32%) , 7p , 9q , 17p , 20q (each 27%), and 12q and Xp (each 25%). A correlation was found between the total number of genetic changes per tumor and both tumor size and disease stage. In particular , losses of 3p and 6 and gains of 14q and Xq were found to be associated with metastatic disease. Furthermore , characteristic patterns of genetic changes were found in the various EPT subtypes , eg , 6q loss in malignant insulinomas , indicating that these groups might evolve along genetically different pathways. The highlighted genetic aberrations , including the newly found involvement of 6q losses and sex chromosome alterations , should stimulate the further analysis of these chromosomal regions, which may lead to the discovery of novel genes important in the tumorigenesis and evolution of EPTs. (Am J Pathol 1999, 155:1787-1794)

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Section: Discussionsupporting

confidence: 55%

Genetic Differences in Endocrine Pancreatic Tumor Subtypes Detected by Comparative Genomic Hybridization

Speel¹,

Richter²,

Moch³

et al. 1999

The American Journal of Pathology

144

122

View full text Add to dashboard Cite

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“…Specifically, allelic deletions and mutations of the MEN1 gene have been reported in lung carcinoid tumors, including those developing sporadically in the absence of MEN1 syndrome (17,20,24). These alterations appear to be important in cancer pathogenesis and to affect additional genes telomerically to the MEN1 gene (8,9).…”

Section: Discussionsupporting

confidence: 85%

“…We also analysed D11S906, which is located telomerically to the MEN1 gene and is a locus that has not been analyzed intensely in sporadic lung carcinoids, despite preliminary indications that it may label a locus with oncosuppresive activity (8,20,31). LOH at D11S906 was previously shown in >50% of the cases (20,24) while MI has been reported in a single case (24).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that there is an independent locus with oncosuppressive activity, on 11q telomerically to the MEN1 gene (8). We have noticed that D11S906 showed frequent existence of allelic loss or MI.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

“…Loss of heterozygosity (LOH) studies attributed tumor suppressing function to the MEN1 gene region, telomerically to PYGM (5)(6)(7). Other LOH studies suggest the presence of another tumor suppressor gene close to the MEN1 gene (8,9).…”

Section: Introductionmentioning

confidence: 99%

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Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: A novel approach using real-time PCR with melting curve analysis in histopathologic material

Vageli¹,

Daniil²,

Dahabreh³

et al. 2006

Oncol Rep

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Abstract. The possible causes and genetic mechanisms of pulmonary carcinoid tumor development are unclear. In this study, we examined genetic alterations at the MEN1 locus in archival material from 15 pulmonary carcinoids. We employed, for the first time in this setting, real-time PCR with melting curve analysis in order to identify loss of heterozygosity (LOH) or microsatellite instability (MI) in two polymorphic markers (PYGM, D11S449) at the MEN1 locus and one additional marker (D11S906) of a putative oncosuppressive region distal to the MEN1 gene. Sequencing data were available in a selected subset of tumors in order to verify the reliability of real-time PCR analysis. We observed LOH at PYGM in 38% of the cases and MI in 13.3% of the cases. Our data indicate that real-time PCR with melting curve analysis is a reliable technique for LOH and MI detection and indicate that genetic errors at the MEN1 locus but also distal to it may be involved in the development of sporadic pulmonary carcinoid tumors.

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Sporadic follicular thyroid tumors show loss of a 200-kb region in 11q13 without evidence for mutations in theMEN1 gene

Nord

Wong

Wallin

et al. 1999

Genes Chromosom. Cancer

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Loss of heterozygosity (LOH) in 11q13 where the tumor suppressor gene for multiple endocrine neoplasia type 1 (MEN 1) is located has been demonstrated in several tumor types, including follicular thyroid tumors, but whether the MEN1 gene is actually involved in their tumorigenesis is not known. In the present study, the involvement of the MEN1 gene in follicular thyroid tumors was investigated. By using 14 MEN1‐linked microsatellite markers, LOH was demonstrated in 12 out of 60 follicular thyroid tumors: 2/18 adenomas, 4/15 atypical adenomas, 1/6 Hürthle cell adenomas, 1/9 carcinomas, 3/6 Hürthle cell carcinomas, and 1/6 anaplastic carcinomas. In the tumors with LOH, a single minimal region of overlapping deletions was mapped to the 200‐kb interval between D11S4946 and D11S4939. Tumors that showed 11q13 LOH were screened for mutations of the MEN1 gene using single‐strand conformation analysis. Abnormal shifts detected in seven tumors in two exons were sequenced, which revealed two different polymorphisms present in both tumor and constitutional DNA, but without somatic mutation. Taken together, these results suggest that in this region, a tumor suppressor gene other than MEN1 might be involved in the tumorigenesis of follicular thyroid tumors. Genes Chromosomes Cancer 26:35–39, 1999. © 1999 Wiley‐Liss, Inc.

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Deletion mapping of endocrine tumors localizes a second tumor suppressor gene on chromosome band 11q13

Cited by 69 publications

References 28 publications

Genetic Differences in Endocrine Pancreatic Tumor Subtypes Detected by Comparative Genomic Hybridization

Genetic Differences in Endocrine Pancreatic Tumor Subtypes Detected by Comparative Genomic Hybridization

Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: A novel approach using real-time PCR with melting curve analysis in histopathologic material

Sporadic follicular thyroid tumors show loss of a 200-kb region in 11q13 without evidence for mutations in theMEN1 gene

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