DEVELOPMENTAL DEFECTS IN GORLIN SYNDROME RELATED TO A PUTATIVE TUMOR SUPPRESSOR GENE ON CHROMOSOME-9

被引:355
作者
GAILANI, MR
BALE, SJ
LEFFELL, DJ
DIGIOVANNA, JJ
PECK, GL
POLIAK, S
DRUM, MA
PASTAKIA, B
MCBRIDE, OW
KASE, R
GREENE, M
MULVIHILL, JJ
BALE, AE
机构
[1] NIH, CTR CLIN, DEPT RADIOL, BETHESDA, MD 20892 USA
[2] WESTAT CORP, ROCKVILLE, MD 20852 USA
[3] YALE UNIV, SCH MED, DEPT DERMATOL, NEW HAVEN, CT 06510 USA
[4] NCI, ENVIRONM EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA
[5] NIDR, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA
[6] NCI, DERMATOL BRANCH, BETHESDA, MD 20892 USA
[7] NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA
[8] NCI, CLIN EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA
关键词
D O I
10.1016/0092-8674(92)90122-S
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Gorlin syndrome is an autosomal dominant disorder that predisposes to basal cell carcinomas of the skin, ovarian fibromas, and medulloblastomas. Unlike other hereditary disorders associated with cancer, it features widespread developmental defects. To investigate the possibility that the syndrome is caused by mutation in a tumor suppressor gene, we searched for loss of heterozygosity in 16 sporadic basal cell carcinomas, 2 hereditary basal cell carcinomas, and 1 hereditary ovarian fibroma and performed genetic linkage studies in five Gorlin syndrome kindreds. Eleven sporadic basal cell carcinomas and all 3 hereditary tumors had allelic loss of chromosome 9q31, and all informative kindreds showed tight linkage between the Gorlin syndrome gene and a genetic marker in this region. Loss of heterozygosity at this chromosomal location, particularly in hereditary tumors, implies that the gene is homozygously inactivated and normally functions as a tumor suppressor. In contrast, hemizygous germline mutations lead to multiple congenital anomalies.
引用
收藏
页码:111 / 117
页数:7
相关论文
共 49 条
  • [1] ANDERSON MA, 1984, IN VITRO CELL DEV B, V20, P856
  • [2] APPLEGATE LA, 1990, CANCER RES, V50, P637
  • [3] SISTER CHROMATID EXCHANGE AND CHROMOSOME FRAGILITY IN THE NEVOID BASAL-CELL CARCINOMA SYNDROME
    BALE, AE
    BALE, SJ
    MURLI, H
    IVETT, J
    MULVIHILL, JJ
    PARRY, DM
    [J]. CANCER GENETICS AND CYTOGENETICS, 1989, 42 (02) : 273 - 279
  • [4] RELATIONSHIP BETWEEN HEAD CIRCUMFERENCE AND HEIGHT IN NORMAL ADULTS AND IN THE NEVOID BASAL-CELL CARCINOMA SYNDROME AND NEUROFIBROMATOSIS TYPE-I
    BALE, SJ
    AMOS, CI
    PARRY, DM
    BALE, AE
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS, 1991, 40 (02): : 206 - 210
  • [5] HYPOSENSITIVITY OF BASAL-CELL NEVUS SYNDROME DERMAL FIBROBLASTS TO ULTRAVIOLET-A
    BASSUKAS, ID
    SCHELL, H
    ARAI, A
    HOFMANN, P
    [J]. LANCET, 1990, 336 (8718) : 825 - 825
  • [6] A ROLE FOR SUNLIGHT IN SKIN-CANCER - UV-INDUCED P53 MUTATIONS IN SQUAMOUS-CELL CARCINOMA
    BRASH, DE
    RUDOLPH, JA
    SIMON, JA
    LIN, A
    MCKENNA, GJ
    BADEN, HP
    HALPERIN, AJ
    PONTEN, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (22) : 10124 - 10128
  • [7] EXPRESSION OF RECESSIVE ALLELES BY CHROMOSOMAL MECHANISMS IN RETINOBLASTOMA
    CAVENEE, WK
    DRYJA, TP
    PHILLIPS, RA
    BENEDICT, WF
    GODBOUT, R
    GALLIE, BL
    MURPHREE, AL
    STRONG, LC
    WHITE, RL
    [J]. NATURE, 1983, 305 (5937) : 779 - 784
  • [8] CHAN GL, 1983, AM J PATHOL, V111, P50
  • [9] FEARS TR, 1982, JNCI-J NATL CANCER I, V69, P365
  • [10] FEATHERSTONE T, 1983, AM J HUM GENET, V35, P58