Genomic imbalances detected by comparative genomic hybridization are prognostic markers in invasive ductal breast carcinomas

Zudaire, Isabel; Odero, Marı́a D.; Caballero, Carmela; Valenti, Catherine; Martínez-Peñuela, J.M.; Isola, Jorma; Calasanz, Marı́a José

doi:10.1046/j.1365-2559.2002.01413.x

Cited by 41 publications

(36 citation statements)

References 36 publications

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“…In a study of T2 (42 cm) nodenegative breast cancers, a high overall number of genetic aberrations was correlated with poor prognosis, and an increased copy number at 8q and 20q13 indicated an aggressive phenotype (Isola et al, 1995). Another similar study of invasive ductal carcinomas found that gains on 1q, 11q, 17q, and 20q were associated with poor prognosis (Zudaire et al, 2002). These DNA changes were common in our series as well, and this observation is in agreement with the more aggressive clinical course of premenopausal breast cancer.…”

Section: Discussionsupporting

confidence: 91%

“…Likewise, our study may be the first to screen for somatic genetic changes specifically in premenopausal tumours, providing new insight into the molecular pathology of early-onset breast cancer. The average number of total CNAs in our cohort of tumours was 76 (range 35 -134), which is approximately eight times the average number of CNAs in breast cancers detected by conventional CGH (Isola et al, 1995;Kuukasjärvi et al, 1997;Aubele et al, 2000a, b;Zudaire et al, 2002), demonstrating the superior sensitivity of our assay. This is in keeping with the density of the BAC arrays used (some 3000 elements, average resolution B1 Mb).…”

Section: Discussionmentioning

confidence: 55%

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Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York

Varma

Huang

et al. 2005

Br J Cancer

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High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35 -134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 55%

Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York

Varma

Huang

et al. 2005

Br J Cancer

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“…Compared with previously published reports on female breast cancer, [16][17][18][19] our results demonstrate that across the genome there is a marked similarity between the somatic genetic changes in male and female breast cancer (Fig. 2).…”

Section: Discussionsupporting

confidence: 49%

“…For comparison, a reference CGH data set of 239 female breast cancers compiled from 4 different studies providing full karyotype descriptions was used. [16][17][18][19] For better comparability, only histological types that were also represented in the present series of male breast cancer were included. All statistical analyses were performed using the software system R. 20 The level of significance was set at 0.05.…”

Section: Discussionmentioning

confidence: 99%

Comparative genomic hybridization analysis on male breast cancer

Rudlowski

Schulten

Golas

et al. 2006

Intl Journal of Cancer

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The spectrum of genetic alterations in primary male breast cancer is not well established. We analyzed chromosomal imbalances in 39 tumor samples from primary male breast cancer by comparative genomic hybridization (CGH) and correlated CGH findings with clinicopathological factors. Chromosomal gains were most frequent at 1q (46%), 8q (46%), 16p (36%), 17q (36%), Xq (28%), 20q (26%) and Xp (18%). Losses were most commonly observed at 8p (36%), 16q (28%), 13q (28%), 6q (18%), 11q (18%) and 22q (18%). Gains at 16p, 20q and Xq and losses at 13q correlated significantly with higher degree of cytogenetic complexity. Significant associations with clinicopathological factors were observed for 18q and 216q with larger tumor size and 216q with lower proliferative activity and lower grade of malignancy. A comparison with reported CGH data from female breast cancer showed a similar pattern of chromosomal imbalances, including 11q, 28p, 18q, 213q, 116p, 216q, 117q and 120q. Our results indicate that male breast cancer shares a common pattern of imbalances with female breast cancer, suggesting that similar genetic events may underlie the development and progression of male and female breast cancer. ' 2005 Wiley-Liss, Inc.Key words: male breast cancer; comparative genomic hybridization; genomic aberrations Male breast cancer is an uncommon disease, accounting for 1% of all breast cancer cases. 1 The phenotypic characteristics are not well studied, and are mainly inferred from female breast cancer. Although both diseases share similarities, there are notable differences in risk factors, prognosis and survival. 2 Most male breast cancers are estrogen receptor (ER) and progesterone receptor (PR) positive 1 and expression levels of the HER-2/neu receptor are typically low. 3 The vast majority are ductal tumors and lobular tumors are rare. 4 The comparably unfavorable outcome in male breast cancer has been attributed to more advanced local tumor stages and high incidence of lymph node invasion. It has been postulated that close proximity to skin and nipple facilitates early invasion of lymph vessels, leading to earlier regional and distant metastasis. 5 Germline BRCA2 mutations account for a significant part of male breast cancer, but the majority of patients lack a known inherited predisposition. 6 As in women, axillary lymph node status, tumor size, histological grade and hormone receptor status have been proposed to be the prognostic factors in men with breast cancer. 1 Data regarding more recent molecular markers and their prognostic significance in male breast cancer are limited. The identification of genetic changes and new molecular markers in male breast cancer may provide insights into the biologic differences between male and female breast cancer patients and could aid in clinical management. 7 So far, data on the presence of specific genetic alterations in male breast cancer are limited. Most of these studies are focused on the analysis of germline mutations.No comprehensive molecular cytogenetic study on male breast ca...

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“…This is in line with findings in female breast cancer. 25 When loss of 16q and gain of 16p were both present, the correlation was even stronger (n ¼ 112; P ¼ 0.012). However, other than in female breast cancer, we found no or few correlations between 16q loss and other favorable clinicopathological features such as low grade, low mitotic count, or small tumor size in male breast cancer.…”

Section: Discussionmentioning

confidence: 96%

Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification

et al. 2013

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Gene copy number changes have an important role in carcinogenesis and could serve as potential biomarkers for prognosis and targets for therapy. Copy number changes mapping to chromosome 16 have been reported to be the most frequent alteration observed in female breast cancer and a loss on 16q has been shown to be associated with low grade and better prognosis. In the present study, we aimed to characterize copy number changes on 16q in a group of 135 male breast cancers using a novel multiplex ligation-dependent probe amplification kit. One hundred and twelve out of 135 (83%) male breast cancer showed copy number changes of at least one gene on chromosome 16, with frequent loss of 16q (71/135; 53%), either partial (66/135; 49%) or whole arm loss (5/135; 4%). Losses on 16q were thereby less often seen in male breast cancer than previously described in female breast cancer. Loss on 16q was significantly correlated with favorable clinicopathological features such as negative lymph node status, small tumor size, and low grade. Copy number gain of almost all genes on the short arm was also significantly correlated with lymph node negative status. A combination of 16q loss and 16p gain correlated even stronger with negative lymph node status (n ¼ 112; P ¼ 0.012), which was also underlined by unsupervised clustering. In conclusion, copy number loss on 16q is less frequent in male breast cancer than in female breast cancer, providing further evidence that male breast cancer and female breast cancer are genetically different. Gain on 16p and loss of 16q identify a group of male breast cancer with low propensity to develop lymph node metastases.

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Genomic imbalances detected by comparative genomic hybridization are prognostic markers in invasive ductal breast carcinomas

Cited by 41 publications

References 36 publications

Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York

Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York

Comparative genomic hybridization analysis on male breast cancer

Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification

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