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Genomic landscape of ductal carcinoma in situ and association with progression.
- Source :
-
Breast cancer research and treatment [Breast Cancer Res Treat] 2019 Nov; Vol. 178 (2), pp. 307-316. Date of Electronic Publication: 2019 Aug 17. - Publication Year :
- 2019
-
Abstract
- Purpose: The detection rate of breast ductal carcinoma in situ (DCIS) has increased significantly, raising the concern that DCIS is overdiagnosed and overtreated. Therefore, there is an unmet clinical need to better predict the risk of progression among DCIS patients. Our hypothesis is that by combining molecular signatures with clinicopathologic features, we can elucidate the biology of breast cancer progression, and risk-stratify patients with DCIS.<br />Methods: Targeted exon sequencing with a custom panel of 223 genes/regions was performed for 125 DCIS cases. Among them, 60 were from cases having concurrent or subsequent invasive breast cancer (IBC) (DCIS + IBC group), and 65 from cases with no IBC development over a median follow-up of 13 years (DCIS-only group). Copy number alterations in chromosome 1q32, 8q24, and 11q13 were analyzed using fluorescence in situ hybridization (FISH). Multivariable logistic regression models were fit to the outcome of DCIS progression to IBC as functions of demographic and clinical features.<br />Results: We observed recurrent variants of known IBC-related mutations, and the most commonly mutated genes in DCIS were PIK3CA (34.4%) and TP53 (18.4%). There was an inverse association between PIK3CA kinase domain mutations and progression (Odds Ratio [OR] 10.2, p < 0.05). Copy number variations in 1q32 and 8q24 were associated with progression (OR 9.3 and 46, respectively; both p < 0.05).<br />Conclusions: PIK3CA kinase domain mutations and the absence of copy number gains in DCIS are protective against progression to IBC. These results may guide efforts to distinguish low-risk from high-risk DCIS.
- Subjects :
- Aged
Aged, 80 and over
Carcinoma, Ductal, Breast therapy
DNA Copy Number Variations
Female
Genetic Predisposition to Disease
Humans
In Situ Hybridization, Fluorescence
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Tumor Burden
Carcinoma, Ductal, Breast genetics
Carcinoma, Ductal, Breast pathology
Carcinoma, Intraductal, Noninfiltrating genetics
Carcinoma, Intraductal, Noninfiltrating pathology
Genome-Wide Association Study methods
Genomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7217
- Volume :
- 178
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Breast cancer research and treatment
- Publication Type :
- Academic Journal
- Accession number :
- 31420779
- Full Text :
- https://doi.org/10.1007/s10549-019-05401-x