MOLECULAR-BIOLOGY OF BREAST-CANCER

被引:8
作者
LEMOINE, NR
机构
关键词
BREAST CANCER; MOLECULAR GENETICS; ONCOGENES; TUMOR SUPPRESSOR GENES;
D O I
10.1093/annonc/5.suppl_4.S31
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: A gene responsible for an inherited predisposition to breast and ovarian cancer has been localized to the long arm of chromosome 17 and termed BRCA1. As well as being closely linked to breast/ovarian cancer cases, this gene may be involved in up to 45% of site-specific breast cancers. The identification and cloning of the BRCA1 gene is imminent, and will facilitate the screening and counselling of families at risk of breast cancer, and in the longer term may open up new therapeutic possibilities. The tumour suppressor gene TP53 is mutated in 25%-40% of cases of sporadic breast cancer, and is associated with an aggressive tumour phenotype and poor prognosis in both node-positive and node-negative cases. The pattern of mutations in this tumour suppressor gene shows a higher than expected frequency of G to T transversions, mostly restricted to the highly conserved domain in exons 5 to 8. In many, but not all cases, point mutation of one allele is accompanied by deletion of the remaining normal allele at chromosome 17p13. Abnormalities of TP53 appear to be relatively early events in tumorigenesis, being present in ductal carcinoma in situ lesions. The retinoblastoma gene RB1 shows a variety of abnormalities in about 20% of breast cancers, and there may be an association with TP53 mutations. Other abnormalities which occur with a particularly high incidence in breast cancer include allele loss at chromosome 1p/1q, 3p, 6q, 11p, 16q and 18q. The ERBB2 oncogene encodes a transmembrane receptor tyrosine kinase whose ligand has recently been claimed to be the heregulin family in man. Overexpression of ERBB2 is a marker of poor prognosis in both node-positive and nodenegative disease, and also a marker of poor response to endocrine therapy and conventional cytotoxic therapy. A number of specific therapies are being developed against this oncoprotein including inhibitory monoclonal antibodies, tyrosine kinase inhibitors, dimerization inhibitors and antisense technology. New development: The identification of a novel transcription factor (OB2-1), which appears to be an important contributor to ERBB2 overexpression in breast cancer, has been an exciting development, which may also present therapeutic possibilities.
引用
收藏
页码:S31 / S37
页数:7
相关论文
共 106 条
  • [1] PRESENCE OF 2 MEMBERS OF C-ERBA RECEPTOR GENE FAMILY (C-ERBA-BETA AND C-ERBA2) IN SMALLEST REGION OF SOMATIC HOMOZYGOSITY ON CHROMOSOME 3P21-P25 IN HUMAN-BREAST CARCINOMA
    ALI, IU
    LIDEREAU, R
    CALLAHAN, R
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1989, 81 (23) : 1815 - 1820
  • [2] REDUCTION TO HOMOZYGOSITY OF GENES ON CHROMOSOME-11 IN HUMAN-BREAST NEOPLASIA
    ALI, IU
    LIDEREAU, R
    THEILLET, C
    CALLAHAN, R
    [J]. SCIENCE, 1987, 238 (4824) : 185 - 188
  • [3] ASSOCIATION OF P53 PROTEIN EXPRESSION WITH TUMOR-CELL PROLIFERATION RATE AND CLINICAL OUTCOME IN NODE-NEGATIVE BREAST-CANCER
    ALLRED, DC
    CLARK, GM
    ELLEDGE, R
    FUQUA, SAW
    BROWN, RW
    CHAMNESS, GC
    OSBORNE, CK
    MCGUIRE, WL
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (03) : 200 - 206
  • [4] GENETIC ALTERATIONS OF THE TUMOR SUPPRESSOR GENE REGIONS 3P, 11P, 13Q, 17P, AND 17Q IN HUMAN BREAST CARCINOMAS
    ANDERSEN, TI
    GAUSTAD, A
    OTTESTAD, L
    FARRANTS, GW
    NESLAND, JM
    TVEIT, KM
    BORRESEN, AL
    [J]. GENES CHROMOSOMES & CANCER, 1992, 4 (02) : 113 - 121
  • [5] EFFICIENT IMMORTALIZATION OF LUMINAL EPITHELIAL-CELLS FROM HUMAN MAMMARY-GLAND BY INTRODUCTION OF SIMIAN VIRUS-40 LARGE TUMOR-ANTIGEN WITH A RECOMBINANT RETROVIRUS
    BARTEK, J
    BARTKOVA, J
    KYPRIANOU, N
    LALANI, EN
    STASKOVA, Z
    SHEARER, M
    CHANG, S
    TAYLORPAPADIMITRIOU, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (09) : 3520 - 3524
  • [6] SELECTIVE IMMORTALIZATION OF A PHENOTYPICALLY DISTINCT EPITHELIAL-CELL TYPE BY MICROINJECTION OF SV40 DNA INTO CULTURED HUMAN-MILK CELLS
    BARTEK, J
    BARTKOVA, J
    LALANI, EN
    BREZINA, V
    TAYLORPAPADIMITRIOU, J
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1990, 45 (06) : 1105 - 1112
  • [7] MORPHOLOGICAL-DIFFERENTIATION OF HYBRIDS OF HUMAN MAMMARY EPITHELIAL-CELL LINES IS DOMINANT AND CORRELATES WITH THE PATTERN OF EXPRESSION OF INTERMEDIATE FILAMENTS
    BERDICHEVSKY, F
    TAYLORPAPADIMITRIOU, J
    [J]. EXPERIMENTAL CELL RESEARCH, 1991, 194 (02) : 267 - 274
  • [8] BERDICHEVSKY F, 1992, J CELL SCI, V102, P437
  • [9] BEVILACQUA G, 1989, CANCER RES, V49, P5185
  • [10] THE SEARCH FOR THE FAMILIAL BREAST OVARIAN-CANCER GENE
    BLACK, DM
    SOLOMON, E
    [J]. TRENDS IN GENETICS, 1993, 9 (01) : 22 - 26