Absence of CCND1 gene amplification in breast tumours of BRCA1 mutation carriers

Vaziri, S. A.; Rr, Tubbs; Darlington, Gerarda; Casey, Graham

doi:10.1136/mp.54.4.259

Cited by 43 publications

(33 citation statements)

References 22 publications

(13 reference statements)

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“…82,83 The majority of tumors arising in BRCA1 germ-line mutation carriers, in particular those diagnosed before 50 years of age, have morphological features similar to those described in basal-like cancers 84,85 and show a basal-like phenotype as defined by immunohistochemistry 86,87 or expression arrays. 8 Both basal-like breast cancers and tumors arising in BRCA1 germ-line mutation carriers show a peculiar pattern of cell-cycle protein expression; 54,84,88,89 both rarely harbor CCND1 gene amplification; 54,88 however, they express significantly lower levels of p27, 84,89 and higher levels of Skp2, 84,89 cyclin E, 84,89 and caspase-3, 89 when compared with sporadic breast carcinomas and BRCA2 mutation tumors.…”

Section: S Badve Et Almentioning

confidence: 99%

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

et al. 2011

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Breast cancer is a heterogeneous disease encompassing a variety of entities with distinct morphological features and clinical behaviors. Although morphology is often associated with the pattern of molecular aberrations in breast cancers, it is also clear that tumors of the same histological type show remarkably different clinical behavior. This is particularly true for 'basal-like cancer', which is an entity defined using gene expression analysis. The purpose of this article was to review the current state of knowledge of basal-like breast cancers, to discuss the relationship between basal-like and triple-negative breast cancers, and to clarify practical implications of these diagnoses for pathologists and oncologists.

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Section: S Badve Et Almentioning

confidence: 99%

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

et al. 2011

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“…The incidence of over-expression of the HER2/neu and cyclin D1 proteins is even higher (about 25-30% and 30-40%, respectively); and these two genes are thought to function as essential oncogenes during the development of a subset of human breast cancer cases (reviewed in Barnes and Gillett, 1998;Lohrisch and Piccart, 2001). In contrast, BRCA1 mutant breast cancers rarely exhibit amplification of the HER2/ neu or cyclin D1 genes and show a very low incidence of HER2/Neu and cyclin D1 protein over-expression (Vaziri et al, 2001;Grushko et al, 2002;Lakhani et al, 2002). In addition to immunophenotypic characteristics, analysis of human breast cancers by DNA microarray analyses suggest a characteristic pattern of gene expression alterations in BRCA1 vs. BRCA2 cancers (Hedenfalk et al, 2001;van't Veer et al, 2002).…”

Section: Immunophenotype Of Brca1 Mutant Cancersmentioning

confidence: 99%

BRCA1 gene in breast cancer

Rosen

Fan

Pestell

et al. 2003

Journal Cellular Physiology

233

195

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The BRCA1 gene was identified and cloned in 1994 based on its linkage to early onset breast cancer and breast-ovarian cancer syndromes in women. While inherited mutations of BRCA1 are responsible for about 40-45% of hereditary breast cancers, these mutations account for only 2-3% of all breast cancers, since the BRCA1 gene is rarely mutated in sporadic breast cancers. However, BRCA1 expression is frequently reduced or absent in sporadic cancers, suggesting a much wider role in mammary carcinogenesis. Since BRCA1 was cloned in 1994, its molecular function has been the subject of intense investigation. These studies have revealed multiple functions of the BRCA1 that may contribute to its tumor suppressor activity, including roles in: cell cycle progression, several highly specialized DNA repair processes, DNA damage-responsive cell cycle checkpoints, regulation of a set of specific transcriptional pathways, and apoptosis. Many of these functions are linked to protein:protein interactions involving different portions of the 1,863 amino acid (aa) BRCA1 protein. BRCA1 functions in cell cycle progression and the DNA damage response appear to be regulated by distinct and specific phosphorylation events, but the molecular pathways activated by these phosphorylations are only beginning to be unraveled. In addition, the reason that BRCA1 mutation carriers develop specific tumor types (breast and ovarian cancers in women and possibly prostate cancers in men) is not clearly understood. Elucidation of the precise molecular functions of the BRCA1 gene product will greatly enhance our understanding of the pathogenesis of hereditary as well as sporadic mammary carcinogenesis.

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“…Whereas cyclin D1 amplification and/or over-expression are relatively common in sporadic breast cancers, BRCA1 mutant cancers showed no cyclin D1 amplification and low levels of cyclin D1 expression (Osin et al 1998, Armes et al 1999, Vaziri et al 2001. The c-Myc oncogene is amplified in 15-20% of sporadic breast cancers.…”

Section: Clinical Research Epidemiology Of Brca1 Mutant Cancersmentioning

confidence: 99%

BRCA1 in hormonal carcinogenesis: basic and clinical research

Rosen¹,

Fan²,

Isaacs³

2005

Endocr Relat Cancer

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The breast and ovarian cancer susceptibility gene-1 (BRCA1) located on chromosome 17q21 encodes a tumor suppressor gene that functions, in part, as a caretaker gene in preserving chromosomal stability. The observation that most BRCA1 mutant breast cancers are hormone receptor negative has led some to question whether hormonal factors contribute to the etiology of BRCA1-mutant breast cancers. Nevertheless, the caretaker function of BRCA1 is a generic one and does not explain why BRCA1 mutations confer a specific risk for tumor types that are hormoneresponsive or that hormonal factors contribute to the etiology, including those of the breast, uterus, cervix, and prostate. An accumulating body of research indicates that in addition to its wellestablished roles in regulation of the DNA damage response, the BRCA1 protein interacts with steroid hormone receptors (estrogen receptor (ER-a) and androgen receptor (AR)) and regulates their activity, inhibiting ER-a activity and stimulating AR activity. The ability of BRCA1 to regulate steroid hormone action is consistent with clinical-epidemiological research suggesting that: (i) hormonal factors contribute to breast cancer risk in BRCA1 mutation carriers; and (ii) the spectrum of risk-modifying effects of hormonal factors in BRCA1 carriers is not identical to that observed in the general population. These data suggest a model for BRCA1 carcinogenesis in which genomic instability leads to the initiation of cancerous cell clones, while loss of normal restraint on hormonal stimulation of mammary epithelial cell proliferation allows amplification of these pre-existing clones. Further research will be required to substantiate this hypothesis.

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Absence of CCND1 gene amplification in breast tumours of BRCA1 mutation carriers

Cited by 43 publications

References 22 publications

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

BRCA1 gene in breast cancer

BRCA1 in hormonal carcinogenesis: basic and clinical research

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