Genomic landscape of adenoid cystic carcinoma of the breast
| Autor: | Martelotto, Luciano, De Filippo, Maria, Ng, Charlotte KY, Natrajan, Rachael, Fuhrmann, Laetitia, Cyrta, Joanna, Piscuoglio, Salvatore, Wen, Huei-Chi, Lim, Raymond, Shen, Ronglai, Schultheis, Anne, Wen, Y Hannah, Edelweiss, Marcia, Mariani, Odette, Stenman, Göran, Chan, Timothy, Colombo, Pierre-Emmanuel, Norton, Larry, Vincent-Salomon, Anne, Reis-Filho, Jorge, Weigelt, Britta |
|---|---|
| Přispěvatelé: | Memorial Sloane Kettering Cancer Center [New York], Breakthrough Breast Cancer Centre, London Institute of Cancer, Institut Curie [Paris], University of Gothenburg (GU), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM) |
| Rok vydání: | 2015 |
| Předmět: |
DNA Copy Number Variations
Oncogene Proteins Fusion Genes myb MYB-NFIB DNA Mutational Analysis Gene Dosage chemical and pharmacologic phenomena Triple Negative Breast Neoplasms Real-Time Polymerase Chain Reaction Article Gene Frequency Biomarkers Tumor Humans adenoid cystic carcinoma Genetic Predisposition to Disease skin and connective tissue diseases In Situ Hybridization Fluorescence Reverse Transcriptase Polymerase Chain Reaction massively parallel sequencing Genomics Carcinoma Adenoid Cystic Gene Expression Regulation Neoplastic Phenotype Mutation triple-negative breast cancer Female [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | The Journal of pathology and bacteriology The Journal of pathology and bacteriology, John Wiley & Sons, 2015, 237 (2), pp.179-189. ⟨10.1002/path.4573⟩ |
| ISSN: | 1096-9896 0368-3494 1555-2039 |
| Popis: | International audience; Adenoid cystic carcinoma (AdCC) is a rare type of triple-negative breast cancer (TNBC) characterized by the presence of the MYB-NFIB fusion gene. The molecular underpinning of breast AdCCs other than the MYB-NFIB fusion gene remains largely unexplored. Here we sought to define the repertoire of somatic genetic alterations of breast AdCCs. We performed whole-exome sequencing, followed by orthogonal validation, of 12 breast AdCCs to determine the landscape of somatic mutations and gene copy number alterations. Fluorescence in situ hybridization and reverse-transcription PCR were used to define the presence of MYB gene rearrangements and MYB-NFIB chimeric transcripts. Unlike common forms of TNBC, we found that AdCCs have a low mutation rate (0.27 non-silent mutations/Mb), lack mutations in TP53 and PIK3CA and display a heterogeneous constellation of known cancer genes affected by somatic mutations, including MYB, BRAF, FBXW7, SMARCA5, SF3B1 and FGFR2. MYB and TLN2 were affected by somatic mutations in two cases each. Akin to salivary gland AdCCs, breast AdCCs were found to harbour mutations targeting chromatin remodelling, cell adhesion, RNA biology, ubiquitination and canonical signalling pathway genes. We observed that, although breast AdCCs had rather simple genomes, they likely display intra-tumour genetic heterogeneity at diagnosis. Taken together, these findings demonstrate that the mutational burden and mutational repertoire of breast AdCCs are more similar to those of salivary gland AdCCs than to those of other types of TNBCs, emphasizing the importance of histological subtyping of TNBCs. Furthermore, our data provide direct evidence that AdCCs harbour a distinctive mutational landscape and genomic structure, irrespective of the disease site of origin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text