PREDISPOSITION TO RENAL-CARCINOMA IN THE EKER RAT IS DETERMINED BY GERM-LINE MUTATION OF THE TUBEROUS-SCLEROSIS-2 (TSC2) GENE

被引：268

作者：

YEUNG, RS ^{[1
]}

XIAO, GH ^{[1
]}

JIN, F ^{[1
]}

LEE, WC ^{[1
]}

TESTA, JR ^{[1
]}

KNUDSON, AG ^{[1
]}

机构：

[1] FOX CHASE CANC CTR,DIV BASIC SCI,PHILADELPHIA,PA 19111

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1994年 / 91卷 / 24期

关键词：

HEREDITARY CANCER; ANIMAL MODEL; LINKAGE ANALYSIS; TUMOR SUPPRESSOR GENE;

D O I：

10.1073/pnas.91.24.11413

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genetic predisposition to neoplasia often involves tumor suppressor genes. One such model of hereditary renal carcinoma was described in the rat by Eker. These tumors share morphologic similarities with human renal cancer. Linkage analysis localized the inherited mutation to rat chromosome band 10q12. This region is syntenic with human chromosome band 16p13.3, the site of the tuberous sclerosis 2 (TSC2) gene. A specific rearrangement of the rat homologue of TSC2 was found to cosegregate with carriers of the predisposing mutation. Tumors with or without loss of heterozygosity expressed only the mutant allele, consistent with the two-hit hypothesis. This mutation gave rise to an aberrant transcript that deletes the 3' end normally containing a region of homology with the catalytic domain of rap1GAP.

引用

页码：11413 / 11416

页数：4

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