Chromosomal changes in aggressive breast cancers with basal-like features

Yu, Wayne; Kanaan, Yasmine; Baed, Young Kyung; Gabrielson, Edward

doi:10.1016/j.cancergencyto.2009.03.017

Cited by 44 publications

(40 citation statements)

References 34 publications

(31 reference statements)

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“…We compared the findings on our series (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE23891) with those found on a female breast cancer dataset deposited with the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE12659) [32].…”

Section: Discussionmentioning

confidence: 99%

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Gene copy number variation in male breast cancer by aCGH

Tommasi¹,

Mangia²,

Iannelli³

et al. 2011

Cell Oncol.

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Abstract.Background: Male breast cancer (MBC) is a rare disease and little is known about its etiopathogenesis. Array comparative genomic hybridization (aCGH) provides a method to quantitatively measure the changes of DNA copy number and to map them directly onto the complete linear genome sequences. The aim of this study was to investigate DNA imbalances by aCGH and compare them with a female breast cancer dataset.Methods: We used Agilent Human Genome CGH Microarray Kit 44B and 44K to compare genomic alterations in 25 male breast cancer tissues studied at NCC of Bari and 16 female breast cancer deposited with the Gene Expression Omnibus (GSE12659). Data analysis was performed with Nexus Copy Number 5.0 software.Results: All the 25 male and 16 female breast cancer samples displayed some chromosomal instability (110.93 alterations per patient in female, 69 in male). However, male samples presented a lower frequency of genetic alterations both in terms of loss and gains.Conclusion: aCGH is an effective tool for analysis of cytogenetic aberrations in MBC, which involves different biological processes than female. Male most significant altered regions contained genes involved in cell communication, cell division and immunological response, while female cell-cell junction maintenance, regulation of transcription and neuron development.

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Section: Discussionmentioning

confidence: 99%

“…ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12659), to which the same algorithms have been applied [32]. Among datasets available online this has been chosen being, in our opinion, the most comparable to ours in terms of number of cases and platform of analysis.…”

Section: Microarray Data Analysismentioning

confidence: 99%

Gene copy number variation in male breast cancer by aCGH

Tommasi¹,

Mangia²,

Iannelli³

et al. 2011

Cell Oncol.

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“…We have previously shown that high protein expression of VEGFR2 is significantly correlated to poor survival in TNBC (Ryden et al, 2010). Genomic aberrations of VEGFR2 or KIT have not previously been investigated in TNBC tumors, but high-level amplification of the 4q12 region was reported in a small sample set of basal-like breast cancers (Yu et al, 2009). In the present study, we investigated 31 TNBC and 50 non-TNBC tumors for copy number gains of VEGFR2 and KIT, as well as the protein expression of KIT.…”

Section: Discussionmentioning

confidence: 96%

Increased gene copy number of KIT and VEGFR2 at 4q12 in primary breast cancer is related to an aggressive phenotype and impaired prognosis

Johansson

Aaltonen

Ebbesson

et al. 2011

Genes Chromosomes & Cancer

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Triple-negative breast cancer (TNBC) is associated with poor prognosis and no targeted treatments are available for TNBC. Drugs inhibiting tyrosine kinases, such as vascular endothelial growth factor receptor 2 (VEGFR2) and KIT, have shown some promising results for patients with TNBC. The aim of the study was to investigate whether gains and/or amplifications of VEGFR2 and KIT, located at 4q12, occur in TNBC. Fluorescence in situ hybridization (FISH) was used to quantify gene copy numbers of VEGFR2 and KIT in 83 primary human breast cancers including 31 TNBCs. Gains were defined as ≥ 4 gene copies in >40% of the cancer cells, whereas amplification was defined as CEP >2 in more than 10% of the cancer cells. A tumor was considered FISH positive for KIT and/or VEGFR2 if it displayed copy number gain and/or amplification. Ten (32%) of the TNBCs were VEGFR2 FISH positive and nine (29%) were KIT FISH positive, whereas non-TNBCs were FISH positive for VEGFR2 and KIT in nine (18%) cases for both genes, but no significant difference between TNBCs and non-TNBCs was found. FISH positivity for VEGFR2 and KIT was significantly correlated (χ(2) test, P < 0.001), and significantly related to ER negativity and high Nottingham histological grade (NHG). A significantly worse 5-year breast cancer specific survival (BCSS) was seen for FISH positive cases. Increased copy number of VEGFR2 and KIT thus has the potential of functioning as a novel predictive biomarker for selected targeted therapy particularly in the difficult-to-treat TNBC patient category.

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“…In human disease, the mechanisms by which α 2 integrin subunit gene expression is decreased in cancer are unknown. The human α 2 integrin gene lies on chromosome 5q23, a site of frequent deletions in breast cancer (45). However, deletion of the α 2 integrin gene in cancer has not been reported.…”

Section: Figurementioning

confidence: 99%

The α2β1 integrin is a metastasis suppressor in mouse models and human cancer

Ramirez¹,

Zhang²,

Madamanchi³

et al. 2011

J. Clin. Invest.

190

148

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Integrins regulate cell-cell and cell-matrix adhesion and thereby play critical roles in tumor progression and metastasis. Although work in preclinical models suggests that β 1 integrins may stimulate metastasis of a number of cancers, expression of the β 1 subunit alone has not been shown to be a useful prognostic indicator in human cancer patients. Here we have demonstrated that the α 2 β 1 integrin suppresses metastasis in a clinically relevant spontaneous mouse model of breast cancer. These data are consistent with previous studies indicating high expression of α 2 β 1 integrin in normal breast epithelium and loss of α 2 β 1 in poorly differentiated breast cancer. They are also consistent with our systematic analysis of microarray databases of human breast and prostate cancer, which revealed that decreased expression of the gene encoding α 2 integrin, but not genes encoding α 1 , α 3 , or β 1 integrin, was predictive of metastatic dissemination and decreased survival. The predictive value of α 2 expression persisted within both good-risk and poor-risk cohorts defined by estrogen receptor and lymph node status. Thus, the α 2 β 1 integrin functionally inhibits breast tumor metastasis, and α 2 expression may serve as an important biomarker of metastatic potential and patient survival.

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Chromosomal changes in aggressive breast cancers with basal-like features

Cited by 44 publications

References 34 publications

Gene copy number variation in male breast cancer by aCGH

Gene copy number variation in male breast cancer by aCGH

Increased gene copy number of KIT and VEGFR2 at 4q12 in primary breast cancer is related to an aggressive phenotype and impaired prognosis

The α2β1 integrin is a metastasis suppressor in mouse models and human cancer

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