Molecular characterization of the men1 tumor suppressor gene in sporadic pituitary tumors

被引:93
作者
Prezant, TR [1 ]
Levine, J [1 ]
Melmed, S [1 ]
机构
[1] Univ Calif Los Angeles, Cedars Sinai Res Inst, Div Endocrinol & Metab, Los Angeles, CA 90048 USA
关键词
D O I
10.1210/jc.83.4.1388
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Anterior pituitary turners arise sporadically, and also as part of the inherited multiple endocrine neoplasia type I (MEN 1) syndrome. To investigate the role of the recently isolated men1 gene in sporadic pituitary tumorigenesis, the complete coding sequence was screened for mutations in 45 sporadic anterior pituitary tumors, including 14 hormone secreting tumors and 31 nonsecreting tumors, by dideoxy fingerprinting and sequence analysis. No pathogenic sequence changes were found in the men1 coding region. The men1 gene was expressed in 43 of these tumors with sufficient RNA, including one tumor with loss of heterozygosity (LOH) for several polymorphic markers on chromosomal region 11q13. Furthermore, both alleles were expressed in 19 tamers in which the constitutional DNA was heterozygous for intragenic polymorphisms. Thus, inactivation of the men1 tumor suppressor gene, by mutation or by imprinting, does not appear to play a prominent role in sporadic pituitary adenoma pathogenesis.
引用
收藏
页码:1388 / 1391
页数:4
相关论文
共 19 条
[1]   Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states [J].
Agarwal, SK ;
Kester, MB ;
Debelenko, LV ;
Heppner, C ;
EmmertBuck, MR ;
Skarulis, MC ;
Doppman, JL ;
Kim, YS ;
Lubensky, IA ;
Zhuang, ZP ;
Green, JS ;
Guru, SC ;
Manickam, P ;
Olufemi, SE ;
Liotta, LA ;
Chandrasekharappa, SC ;
Collins, FS ;
Spiegel, AM ;
Burns, AL ;
Marx, SJ .
HUMAN MOLECULAR GENETICS, 1997, 6 (07) :1169-1175
[2]   CLINICALLY NONFUNCTIONING PITUITARY-TUMORS ARE MONOCLONAL IN ORIGIN [J].
ALEXANDER, JM ;
BILLER, BMK ;
BIKKAL, H ;
ZERVAS, NT ;
ARNOLD, A ;
KLIBANSKI, A .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (01) :336-340
[3]   Allelic deletion in pituitary adenomas reflects aggressive biological activity and has potential value as a prognostic marker [J].
Bates, AS ;
Farrell, WE ;
Bicknell, EJ ;
McNicol, AM ;
Talbot, AJ ;
Broome, JC ;
Perrett, CW ;
Thakker, RV ;
Clayton, RN .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (03) :818-824
[4]   LOCALIZATION OF THE MEN1 GENE TO A SMALL REGION WITHIN CHROMOSOME 11Q13 BY DELETION MAPPING IN TUMORS [J].
BYSTROM, C ;
LARSSON, C ;
BLOMBERG, C ;
SANDELIN, K ;
FALKMER, U ;
SKOGSEID, B ;
OBERG, K ;
WERNER, S ;
NORDENSKJOLD, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (05) :1968-1972
[5]   Positional cloning of the gene for multiple endocrine neoplasia-type 1 [J].
Chandrasekharappa, SC ;
Guru, SC ;
Manickam, P ;
Olufemi, SE ;
Collins, FS ;
EmmertBuck, MR ;
Debelenko, LV ;
Zhuang, ZP ;
Lubensky, IA ;
Liotta, LA ;
Crabtree, JS ;
Wang, YP ;
Roe, BA ;
Weisemann, J ;
Boguski, MS ;
Agarwal, SK ;
Kester, MB ;
Kim, YS ;
Heppner, C ;
Dong, QH ;
Spiegel, AM ;
Burns, AL ;
Marx, SJ .
SCIENCE, 1997, 276 (5311) :404-407
[6]   PUTATIVE TUMOR-SUPPRESSOR GENE ON CHROMOSOME-11 IS IMPORTANT IN SPORADIC ENDOCRINE TUMOR-FORMATION [J].
EUBANKS, PJ ;
SAWICKI, MP ;
SAMARA, GJ ;
GATTI, R ;
NAKAMURA, Y ;
TSAO, D ;
JOHNSON, C ;
HURWITZ, M ;
WAN, YJY ;
PASSARO, E .
AMERICAN JOURNAL OF SURGERY, 1994, 167 (01) :180-185
[7]   BRCA1 MUTATIONS IN PRIMARY BREAST AND OVARIAN CARCINOMAS [J].
FUTREAL, PA ;
LIU, QY ;
SHATTUCKEIDENS, D ;
COCHRAN, C ;
HARSHMAN, K ;
TAVTIGIAN, S ;
BENNETT, LM ;
HAUGENSTRANO, A ;
SWENSEN, J ;
MIKI, Y ;
EDDINGTON, K ;
MCCLURE, M ;
FRYE, C ;
WEAVERFELDHAUS, J ;
DING, W ;
GHOLAMI, Z ;
SODERKVIST, P ;
TERRY, L ;
JHANWAR, S ;
BERCHUCK, A ;
IGLEHART, JD ;
MARKS, J ;
BALLINGER, DG ;
BARRETT, JC ;
SKOLNICK, MH ;
KAMB, A ;
WISEMAN, R .
SCIENCE, 1994, 266 (5182) :120-122
[8]  
Greenman Y, 1996, ANNU REV MED, V47, P95
[9]   Somatic mutation of the MEN1 gene in parathyroid tumours [J].
Heppner, C ;
Kester, MB ;
Agarwal, SK ;
Debelenko, LV ;
EmmertBuck, MR ;
Guru, SC ;
Manickam, P ;
Olufemi, SE ;
Skarulis, MC ;
Doppman, JL ;
Alexander, RH ;
Kim, YS ;
Saggar, SK ;
Lubensky, IA ;
Zhuang, ZP ;
Liotta, LA ;
Chandrasekharappa, SC ;
Collins, FS ;
Spiegel, AM ;
Burns, AL ;
Marx, SJ .
NATURE GENETICS, 1997, 16 (04) :375-378
[10]   CLONAL ORIGIN OF PITUITARY-ADENOMAS [J].
HERMAN, V ;
FAGIN, J ;
GONSKY, R ;
KOVACS, K ;
MELMED, S .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1990, 71 (06) :1427-1433