Back to Search
Start Over
Clinical and molecular relevance of mutant-allele tumor heterogeneity in breast cancer.
- Source :
-
Breast cancer research and treatment [Breast Cancer Res Treat] 2017 Feb; Vol. 162 (1), pp. 39-48. Date of Electronic Publication: 2017 Jan 16. - Publication Year :
- 2017
-
Abstract
- Purpose: Intra-tumor heterogeneity (ITH) plays a pivotal role in driving breast cancer progression and therapeutic resistance. We used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and explored its correlation with clinical parameters and multi-omics data.<br />Methods: We assessed 916 female breast cancer patients from The Cancer Genome Atlas. We calculated the MATH values from whole-exome sequencing data and further investigated their correlation with clinical characteristics, somatic mutations, somatic copy number alterations (SCNAs), and gene enrichment.<br />Results: The patients were divided into low, intermediate, and high MATH groups. High T stage, African American race, and triple-negative or basal-like subtype were associated with a higher MATH level (all P < 0.001). In hormone receptor-positive and human epidermal growth factor receptor-negative patients, the high MATH group showed a tendency toward a worse overall survival (P = 0.052); Furthermore, the TP53 mutation rate increased as MATH was elevated (P < 0.001), whereas CDH1 mutations were correlated with a lower level of MATH (P = 0.002). Several focal and arm-level SCNA events were more common in the high MATH group (P < 0.05), including Chr8q24 with only the MYC gene in the "peak" region. Similarly, high MATH was associated with gene set enrichment related to the MYC pathway and proliferation.<br />Conclusion: Our integrative analysis reveals the clinical and genetic relevance of ITH in breast cancer. These results also suggest the origin and natural history of clonal evolution and intra-tumor genetic heterogeneity, which warrant further investigation.
- Subjects :
- Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Breast Neoplasms mortality
Breast Neoplasms pathology
Computational Biology methods
DNA Copy Number Variations
Databases, Genetic
Female
Humans
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Prognosis
Exome Sequencing
Young Adult
Alleles
Breast Neoplasms genetics
Genetic Association Studies
Genetic Heterogeneity
Genetic Predisposition to Disease
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7217
- Volume :
- 162
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Breast cancer research and treatment
- Publication Type :
- Academic Journal
- Accession number :
- 28093659
- Full Text :
- https://doi.org/10.1007/s10549-017-4113-z