Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17475
Title: Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer.
Authors: Pang, Jia-Min B;Savas, Peter;Fellowes, Andrew P;Mir Arnau, Gisela;Kader, Tanjina;Vedururu, Ravikiran;Hewitt, Chelsee;Takano, Elena A;Byrne, David J;Choong, David Yh;Millar, Ewan Ka;Lee, C Soon;O'Toole, Sandra A;Lakhani, Sunil R;Cummings, Margaret C;Mann, G Bruce;Campbell, Ian G;Dobrovic, Alexander;Loi, Sherene;Gorringe, Kylie L;Fox, Stephen B
Affiliation: Department of Pathology, Peter MacCallum Cancer Centre, Grattan Street, Melbourne, VIC, Australia
Department of Pathology, University of Melbourne, Grattan Street, Parkville, Melbourne, VIC, Australia
Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, Grattan Street, Melbourne, VIC, Australia
Molecular Genomics Core, Peter MacCallum Cancer Centre, Grattan Street, Melbourne, VIC, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Grattan Street, Parkville, Melbourne, VIC, Australia
Cancer Genomics Program, Peter MacCallum Cancer Centre, Grattan Street, Melbourne, VIC, Australia
Translational Breast Cancer Research, The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
Department of Anatomical Pathology, South Eastern Area Pathology Service, St George Hospital, Kogarah, NSW, Australia
School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia
Discipline of Pathology, School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
Cancer Pathology, Bosch Institute, University of Sydney, Camperdown, NSW, Australia
Sydney Medical School, University of Sydney, Camperdown, NSW, Australia
School of Medicine and UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia
Pathology Queensland, The Royal Brisbane and Women's Hospital, Brisbane, Australia
Breast Service, The Royal Melbourne and Royal Women's Hospitals, Parkville, VIC, Australia
Department of Surgery, University of Melbourne, Grattan Street, Parkville, Melbourne, VIC, Australia
Translational Genomics & Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Issue Date: Jul-2017
EDate: 2017
Citation: Modern pathology 2017; 30(7): 952-963
Abstract: The spectrum of genomic alterations in ductal carcinoma in situ (DCIS) is relatively unexplored, but is likely to provide useful insights into its biology, its progression to invasive carcinoma and the risk of recurrence. DCIS (n=20) with a range of phenotypes was assessed by massively parallel sequencing for mutations and copy number alterations and variants validated by Sanger sequencing. PIK3CA mutations were identified in 11/20 (55%), TP53 mutations in 6/20 (30%), and GATA3 mutations in 9/20 (45%). Screening an additional 91 cases for GATA3 mutations identified a final frequency of 27% (30/111), with a high proportion of missense variants (8/30). TP53 mutations were exclusive to high grade DCIS and more frequent in PR-negative tumors compared with PR-positive tumors (P=0.037). TP53 mutant tumors also had a significantly higher fraction of the genome altered by copy number than wild-type tumors (P=0.005), including a significant positive association with amplification or gain of ERBB2 (P<0.05). The association between TP53 mutation and ERBB2 amplification was confirmed in a wider DCIS cohort using p53 immunohistochemistry as a surrogate marker for TP53 mutations (P=0.03). RUNX1 mutations and MAP2K4 copy number loss were novel findings in DCIS. Frequent copy number alterations included gains on 1q, 8q, 17q, and 20q and losses on 8p, 11q, 16q, and 17p. Patterns of genomic alterations observed in DCIS were similar to those previously reported for invasive breast cancers, with all DCIS having at least one bona fide breast cancer driver event. However, an increase in GATA3 mutations and fewer copy number changes were noted in DCIS compared with invasive carcinomas. The role of such alterations as prognostic and predictive biomarkers in DCIS is an avenue for further investigation.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17475
DOI: 10.1038/modpathol.2017.21
ORCID: 0000-0002-8816-1807
0000-0003-1879-2555
0000-0001-5681-2022
0000-0002-7648-8896
PubMed URL: 28338653
Type: Journal Article
Appears in Collections:Journal articles

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