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Sequence analysis and transcript expression of the MEN1 gene in sporadic pituitary tumours.
Br J Cancer. 1999 Apr; 80(1-2):44-50.BJ

Abstract

The majority of pituitary tumours are monoclonal in origin and arise sporadically or occasionally as part of multiple endocrine neoplasia type 1 (MEN1). Whilst a multi-step aetiology involving both oncogenes and tumour suppressor genes has been proposed for their development, the target(s) of these changes are less clearly defined. Both familial and sporadic pituitary tumours have been shown to harbour allelic deletion on 11q13, which is the location of the recently cloned MEN1 gene. We investigated 23 sporadic pituitary tumours previously shown to harbour allelic deletion on 11q13 with the marker PYGM centromeric and within 50 kb of the MEN1 locus. In addition, the use of intragenic polymorphisms in exon 9 and at D11S4946, and of telomeric loci at D11S4940 and D11S4936, revealed that five of 20 tumours had loss of heterozygosity (LOH) telomeric to the menin gene. However, the overall pattern of loss in informative cases was indicative of non-contiguous deletion that brackets the menin gene. Sequence analysis of all MEN1 coding exons and flanking intronic sequence, in tumours and matched patient leucocyte DNA, did not reveal mutation(s) in any of the 23 tumours studied. A benign polymorphism in exon 9 was encountered at the expected frequency, and in seven patients heterozygous for the polymorphism the tumour showed retention of both copies of the menin gene. Reverse transcription polymerase chain reaction analysis of ten evaluable tumours and four normal pituitaries revealed the presence of the menin transcript. Whilst these findings suggest that gene silencing is unlikely to be mechanistic in sporadic pituitary tumorigenesis, they do not exclude changes in the level or stability of the transcript or translation to mature protein. Our study would support and extend very recent reports of a limited role for mutations in the MEN1 gene in sporadic pituitary tumours. Alternatively, these findings may point to an, as yet, unidentified tumour suppressor gene in this region.

Authors+Show Affiliations

Centre for Cell and Molecular Medicine, University of Keele, North Staffs Hospital, Stoke on Trent, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10389976

Citation

Farrell, W E., et al. "Sequence Analysis and Transcript Expression of the MEN1 Gene in Sporadic Pituitary Tumours." British Journal of Cancer, vol. 80, no. 1-2, 1999, pp. 44-50.
Farrell WE, Simpson DJ, Bicknell J, et al. Sequence analysis and transcript expression of the MEN1 gene in sporadic pituitary tumours. Br J Cancer. 1999;80(1-2):44-50.
Farrell, W. E., Simpson, D. J., Bicknell, J., Magnay, J. L., Kyrodimou, E., Thakker, R. V., & Clayton, R. N. (1999). Sequence analysis and transcript expression of the MEN1 gene in sporadic pituitary tumours. British Journal of Cancer, 80(1-2), 44-50.
Farrell WE, et al. Sequence Analysis and Transcript Expression of the MEN1 Gene in Sporadic Pituitary Tumours. Br J Cancer. 1999;80(1-2):44-50. PubMed PMID: 10389976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sequence analysis and transcript expression of the MEN1 gene in sporadic pituitary tumours. AU - Farrell,W E, AU - Simpson,D J, AU - Bicknell,J, AU - Magnay,J L, AU - Kyrodimou,E, AU - Thakker,R V, AU - Clayton,R N, PY - 1999/7/2/pubmed PY - 1999/7/2/medline PY - 1999/7/2/entrez SP - 44 EP - 50 JF - British journal of cancer JO - Br J Cancer VL - 80 IS - 1-2 N2 - The majority of pituitary tumours are monoclonal in origin and arise sporadically or occasionally as part of multiple endocrine neoplasia type 1 (MEN1). Whilst a multi-step aetiology involving both oncogenes and tumour suppressor genes has been proposed for their development, the target(s) of these changes are less clearly defined. Both familial and sporadic pituitary tumours have been shown to harbour allelic deletion on 11q13, which is the location of the recently cloned MEN1 gene. We investigated 23 sporadic pituitary tumours previously shown to harbour allelic deletion on 11q13 with the marker PYGM centromeric and within 50 kb of the MEN1 locus. In addition, the use of intragenic polymorphisms in exon 9 and at D11S4946, and of telomeric loci at D11S4940 and D11S4936, revealed that five of 20 tumours had loss of heterozygosity (LOH) telomeric to the menin gene. However, the overall pattern of loss in informative cases was indicative of non-contiguous deletion that brackets the menin gene. Sequence analysis of all MEN1 coding exons and flanking intronic sequence, in tumours and matched patient leucocyte DNA, did not reveal mutation(s) in any of the 23 tumours studied. A benign polymorphism in exon 9 was encountered at the expected frequency, and in seven patients heterozygous for the polymorphism the tumour showed retention of both copies of the menin gene. Reverse transcription polymerase chain reaction analysis of ten evaluable tumours and four normal pituitaries revealed the presence of the menin transcript. Whilst these findings suggest that gene silencing is unlikely to be mechanistic in sporadic pituitary tumorigenesis, they do not exclude changes in the level or stability of the transcript or translation to mature protein. Our study would support and extend very recent reports of a limited role for mutations in the MEN1 gene in sporadic pituitary tumours. Alternatively, these findings may point to an, as yet, unidentified tumour suppressor gene in this region. SN - 0007-0920 UR - https://www.unboundmedicine.com/medline/citation/10389976/Sequence_analysis_and_transcript_expression_of_the_MEN1_gene_in_sporadic_pituitary_tumours_ L2 - https://doi.org/10.1038/sj.bjc.6690319 DB - PRIME DP - Unbound Medicine ER -