Somatic mutations and human breast cancer. A Status Report

Callahan, Robert; Cropp, Craig S.; Merlo, Giorgio R.; Liscia, Daniel S.; Cappa, Alberto P. M.; Lidereau, Rosette

doi:10.1002/1097-0142(19920315)69:6+<1582::aid-cncr2820691313>3.0.co;2-y

Cited by 81 publications

(29 citation statements)

References 64 publications

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“…Each microdissected specimen was analyzed for LOH at a panel of microsatellite markers chosen from genetic loci previously shown to exhibit high frequency LOH in breast cancer (Aldaz et al, 1995;Brenner and Aldaz, 1997;Callahan et al, 1992). This panel included markers on chromosomes 3p, 9p, 11p, 13q, 16q, 17p, and 17q.…”

Section: Resultsmentioning

confidence: 99%

Genetic Heterogeneity in Ductal Carcinoma of the Breast

Lichy

Dalbègue

Zavar

et al. 2000

Laboratory Investigation

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SUMMARY:Genetic heterogeneity in breast cancer has been observed both by cytogenetic and loss of heterozygosity (LOH) analyses; however, the frequency with which genetically heterogeneous clones arise is unknown. In this study, a panel of 115 breast carcinomas was analyzed to determine the extent of clonal divergence in tumor foci at progressive stages of tumor evolution. Intraductal, infiltrating, and metastatic tumor components were microdissected from each tumor and tested for LOH at 20 microsatellite markers on seven chromosomal arms. Of these cases, 24 (21%) demonstrated genetically divergent clones during tumor progression. Clonal divergence, inferred from discordant LOH patterns, was observed most commonly between intraductal and infiltrating tumor (18 cases), but was also demonstrated between infiltrating and metastatic tumor (11 cases). Discordant LOH was observed with markers on one chromosomal arm in 16 cases, on two in 7 cases, and on four in 1 case, and was observed most commonly with markers on 17p, 17q, and 16q. More detailed microdissection of four cases provided evidence for a specific chronology of genetic alterations occurring during the progression of each tumor. The results indicate that the different tumor components observed microscopically in breast cancer specimens often represent genetically divergent clones. (Lab Invest 2000, 80:291-301).E lucidation of the sequence of genetic events responsible for progression of breast cancer from in situ to infiltrating and metastatic carcinoma is an important goal of efforts to understand the biological basis of this common malignancy. Progression is believed to occur through the accumulation of genetic changes via a process of clonal evolution and clonal selection (Brenner and Aldaz, 1997;Nowell, 1976). Surgically resected breast carcinoma specimens provide a unique resource for analyzing the genetic changes that occur during progression, because specimens typically contain foci of tumor in various stages of progression, including in situ carcinoma, invasive tumor, and lymph node metastases. Morphologically normal epithelial constituents of the breast are usually represented in such specimens, and foci of benign proliferative epithelial lesions may also be present.Detailed studies of colon cancer have shown that adenomatous epithelium adjacent to carcinoma typically has some but not all of the genetic lesions present in the fully developed malignancy, consistent with direct progression from adenoma to carcinoma (Boland et al, 1995;Fearon and Vogelstein, 1990;Vogelstein et al, 1988). By analogy, it might be expected that a similar analysis of breast tumors in different stages of progression would likewise show the accumulation of genetic changes with progression. However, genetic analysis of breast cancer specimens has suggested that the individual foci of tumor identifiable by microscopic examination may not show the precursor-product relationship often observed in colon cancer. Cytogenetic studies in particular have revealed sufficient genetic...

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Section: Resultsmentioning

confidence: 99%

Genetic Heterogeneity in Ductal Carcinoma of the Breast

Lichy

Dalbègue

Zavar

et al. 2000

Laboratory Investigation

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“…The reported p53 mutations in solid tumours ranged from a high of 70% (possibly 100%) in lung cancers to rare occurrences in thyroid and nasopharyngeal carcinomas (Takahashi et al, 1989;Wright et al, 1991;Effert et al, 1992). Similarly, in contrast to the reports of a high percentage of p53 gene alteration and overexpression Bartek et al, 1991;Callahan et al, 1992;Porter et al, 1992), Mazars et al (1992) looked for p53 mutation in over 90 breast carcinomas and could only find mutations in some 20% of the lesions. Accordingly, the incidences of p53 mutations vary greatly between tumour types, geographical locations, as well as from author to author.…”

Section: Function Of the P53mentioning

confidence: 93%

“…They are found in epithelial, mesenchymal, haematopoietic and lymphoid neoplasms as well as in tumours of the central nervous system Chang et al, 1993). Approximately one-half of the adult cancers of the colon Nigro et al, 1989;Shaw et al, 1991) stomach (Tamura et al, 1991), lung Miller et al, 1992), esophagus Bennett et al, 1992), breast Callahan et al, 1992), liver (Bressac et al, 1991;Hsu et al, 1991;Hsia et al, 1992), brain Fults et al, 1992), reticuloendothelial tissues and hematopoietic tissues (Ichikawa et al, 1992;Sugimoto et al, 1992), analysed so far, contain the mutant p53 gene. It should be pointed out, however, that the association between allelic loss and mutation in cell lines is very strong but much less work has been done on solid tumours and it seems that the incidence of p53 mutations in real life is actually much lower than is seen in vitro (Wright et al, 1991;Effert et al, 1992).…”

Section: Function Of the P53mentioning

confidence: 99%

Tumourigenesis associated with the p53 tumour suppressor gene

Chang

Syrjänen²,

Tervahauta³

et al. 1993

Br J Cancer

111

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Summary The p53 gene is contained within 16-20 kb of cellular DNA located on the short arm of human chromosome 17 at position 17pl3.1. This gene encodes a 393-amino-acid nuclear phosphoprotein involved in the regulation of cell proliferation. Current evidence suggests that loss of normal p53 function is associated with cell transformation in vitro and development of neoplasms in vivo. More than 50% of human malignancies of epithelial, mesenchymal, haematopoietic, lymphoid, and central nervous system origin analysed thus far, were shown to contain an altered p53 gene. The oncoproteins derived from several tumour viruses, including the SV40 large T antigen, the adenovirus EIB protein and papillomavirus E6 protein, as well as specific cellular gene products, e.g. murine double minute-2 (MDM2), were found to bind to the wild-type p53 protein and presumably lead to inactivation of this gene product. Therefore, the inactivation of p53 tumour suppressor gene is currently regarded as an almost universal step in the development of human cancers. The current data on p53-associated tumourigenesis are briefly discussed in this minireview.

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“…p53, RB, ER, CerbB-2; have been studied in great detail. [3][4][5] Recent emphasis is on identifying markers related to tumor metastasis, which is the major cause of morbidity and Original Article mortality in these patients'. 6 Certain specific cell-to-cell adhesion molecules have been found to be responsible for embryonic development.…”

Section: Introductionmentioning

confidence: 99%

Expression of E-Cadherin in breast carcinomas and its association with other biological markers — a prospective study

Chintamani

Rekhi

Bansal

et al. 2010

Indian J Surg Oncol

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Context E-cadherin (E-CD) is an important cell adhesion molecule in normal epithelial cells and has been shown to be an invasion tumor suppressor gene. Materials and methods Various clinicopathological parameters like age, family history, tumor stage, histological grade, lymph node status and other biological markers were also analyzed. Present study reveals E-CD expression in 65 cases of breast cancer including 41 (63%) cases of pure infiltrating ductal carcinoma (IDC), 11 (16.9%) of pure infiltrating lobular carcinoma (ILC); another 10 (15.3%) of mixed ductal/lobular type, and remaining 3 (4.6%) miscellaneous types.Results Negative E-CD expression was noticed more in advancing age groups (P = 0.01). About 59.2% cases showing negative E-CD expression had family history of breast and/or other cancers. E-CD expression was found significantly higher in cases of pure IDC (55.5%) than in pure ILC cases (18.1%) (P = 0.04). Eleven (68.7%) of the total 16 high-grade IDC cases, revealed negative expression. Both cases of comedo carcinoma revealed negative expression. Three (30%) out of 10 mixed cases revealed negative expression in both ductal and lobular areas, while in remaining 7 cases, positvity was seen in ductal areas only. Invasive cribriform and medullary carcinoma revealed a stronger expression, while negative staining was observed in sweat gland carcinoma. E-CD re-expression was noticed in lymph node tumor deposits. A direct association of E-CD expression with ER expression and an inverse association with that of p53 were also observed (P = 0.001), (P = 0.04). Conclusions E-CD expression is useful, but limited, in differentiating IDCs from ILCS. Its negative expression correlates with certain poor prognostic parameters reflecting its use as a marker for invasive cancers. It re-expresses at metastatic sites.

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Somatic mutations and human breast cancer. A Status Report

Cited by 81 publications

References 64 publications

Genetic Heterogeneity in Ductal Carcinoma of the Breast

Genetic Heterogeneity in Ductal Carcinoma of the Breast

Tumourigenesis associated with the p53 tumour suppressor gene

Expression of E-Cadherin in breast carcinomas and its association with other biological markers — a prospective study

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