dc.contributor.author | Ng, CKY | |
dc.contributor.author | Martelotto, LG | |
dc.contributor.author | Gauthier, A | |
dc.contributor.author | Wen, H-C | |
dc.contributor.author | Piscuoglio, S | |
dc.contributor.author | Lim, RS | |
dc.contributor.author | Cowell, CF | |
dc.contributor.author | Wilkerson, PM | |
dc.contributor.author | Wai, P | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Arnould, L | |
dc.contributor.author | Geyer, FC | |
dc.contributor.author | Bromberg, SE | |
dc.contributor.author | Lacroix-Triki, M | |
dc.contributor.author | Penault-Llorca, F | |
dc.contributor.author | Giard, S | |
dc.contributor.author | Sastre-Garau, X | |
dc.contributor.author | Natrajan, R | |
dc.contributor.author | Norton, L | |
dc.contributor.author | Cottu, PH | |
dc.contributor.author | Weigelt, B | |
dc.contributor.author | Vincent-Salomon, A | |
dc.contributor.author | Reis-Filho, JS | |
dc.date.accessioned | 2020-07-28T13:36:49Z | |
dc.date.issued | 2015-05-22 | |
dc.identifier.citation | Genome biology, 2015, 16 pp. 107 - ? | |
dc.identifier.issn | 1474-7596 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3881 | |
dc.identifier.eissn | 1474-760X | |
dc.identifier.doi | 10.1186/s13059-015-0657-6 | |
dc.description.abstract | BACKGROUND: HER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous distribution of HER2 gene amplification can be found, which creates clinically challenging scenarios. Currently, breast cancers with HER2 amplification/overexpression in just over 10% of cancer cells are considered HER2-positive for clinical purposes; however, it is unclear as to whether the HER2-negative components of such tumors would be driven by distinct genetic alterations. Here we sought to characterize the pathologic and genetic features of the HER2-positive and HER2-negative components of breast cancers with heterogeneous HER2 gene amplification and to define the repertoire of potential driver genetic alterations in the HER2-negative components of these cases. RESULTS: We separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. In vitro experiments provided functional evidence to suggest that BRF2 and DSN1 overexpression/amplification, and the HER2 I767M mutation may be alterations that compensate for the lack of HER2 amplification in the HER2-negative components of HER2 heterogeneous breast cancers. CONCLUSIONS: Our results indicate that even driver genetic alterations, such as HER2 gene amplification, can be heterogeneously distributed within a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification and HER2 somatic mutations. | |
dc.format | Electronic | |
dc.format.extent | 107 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Receptor, erbB-2 | |
dc.subject | Transcription Factor TFIIIB | |
dc.subject | Chromosomal Proteins, Non-Histone | |
dc.subject | Signal Transduction | |
dc.subject | Gene Amplification | |
dc.subject | Gene Dosage | |
dc.subject | Mutation | |
dc.subject | Female | |
dc.subject | MCF-7 Cells | |
dc.title | Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2015-04-20 | |
rioxxterms.versionofrecord | 10.1186/s13059-015-0657-6 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2015-05-22 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Genome biology | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.publication-status | Published | |
pubs.volume | 16 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Functional Genomics | |
dc.contributor.icrauthor | Natrajan, Rachael | |