Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Vincent-Salomon, A. et al.

Integrated genomic and transcriptomic analysis of ductal carcinoma in situ of the breast.

PURPOSE: To gain insight into genomic and transcriptomic subtypes of ductal carcinomas in situ of the breast (DCIS). EXPERIMENTAL DESIGN: We did a combined phenotypic and genomic analysis of a series of 57 DCIS integrated with gene expression profile analysis for 26 of the 57 cases. RESULTS: Thirty-two DCIS exhibited a luminal phenotype; 21 were ERBB2 positive, and 4 were ERBB2/estrogen receptor (ER) negative with 1 harboring a bona fide basal-like phenotype. Based on a CGH analysis, genomic types were identified in this series of DCIS with the 1q gain/16q loss combination observed in 3 luminal DCIS, the mixed amplifier pattern including all ERBB2, 12 luminal and 2 ERBB2(-)/ER(-) DCIS, and the complex copy number alteration profile encompassing 14 luminal and 1 ERBB2(-)/ER(-) DCIS. Eight cases (8 of 57; 14%) presented a TP53 mutation, all being amplifiers. Unsupervised analysis of gene expression profiles of 26 of the 57 DCIS showed that luminal and ERBB2-amplified, ER-negative cases clustered separately. We further investigated the effect of high and low copy number changes on gene expression. Strikingly, amplicons but also low copy number changes especially on 1q, 8q, and 16q in DCIS regulated the expression of a subset of genes in a very similar way to that recently described in invasive ductal carcinomas. CONCLUSIONS: These combined approaches show that the molecular heterogeneity of breast ductal carcinomas exists already in in situ lesions and further indicate that DCIS and invasive ductal carcinomas share genomic alterations with a similar effect on gene expression profile.[1]

References

Integrated genomic and transcriptomic analysis of ductal carcinoma in situ of the breast. Vincent-Salomon, A., Lucchesi, C., Gruel, N., Raynal, V., Pierron, G., Goudefroye, R., Reyal, F., Radvanyi, F., Salmon, R., Thiery, J.P., Sastre-Garau, X., Sigal-Zafrani, B., Fourquet, A., Delattre, O. Clin. Cancer Res. (2008) [Pubmed]

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