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Title:
Clinical and molecular relevance of mutant-allele tumor heterogeneity in breast cancer | Breast Cancer Research and Treatment
Description:
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. 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. 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 āpeakā region. Similarly, high MATH was associated with gene set enrichment related to the MYC pathway and proliferation. 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.
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Keywords {š}
pubmed, article, cancer, google, scholar, breast, heterogeneity, cas, central, supplementary, material, genetic, math, analysis, data, shao, intratumor, liu, shanghai, csv, tumor, jiang, patients, high, human, genomic, research, clinical, access, nat, privacy, cookies, content, publish, zhiming, genome, somatic, myc, cell, mroz, author, information, search, mutantallele, ding, yizhou, xiyu, progression, atlas, mutations,
Topics {āļø}
pgc-1alpha-responsive genes involved c-myc-induced genomic instability month download article/chapter mutant-allele tumor heterogeneity intra-tumor genetic heterogeneity triple-negative breast cancer intra-tumour heterogeneity zhi-ming shao cancer genome atlas single-cell genetic analysis arm-level scna events intra-tumor heterogeneity machine learning full article pdf breast cancer patients breast cancer 12dz2260100 mootha vk mroz ea human breast tumours primary breast cancer privacy choices/manage cookies promote genomic instability c-myc overexpression african american race related subjects lehmann bd patient informed consent intratumor genetic heterogeneity hormone receptor-positive complex cancer genomics somatic mutation profiles yi-zhou jiang xi-yu liu article ma pan-cancer analysis integrative analysis reveals glioblastoma defines subpopulations article log human cancers intratumoral heterogeneity conserved genomic imbalances shanghai hospitals shdc12010116 shanghai key laboratory shanghai medical college lung cancer breast cancer european economic area reis-filho js activating erbb3 signaling berroa garcia ly
Questions {ā}
- Marusyk A, Almendro V, Polyak K (2012) Intra-tumour heterogeneity: a looking glass for cancer?
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headline:Clinical and molecular relevance of mutant-allele tumor heterogeneity in breast cancer
description: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. 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. 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 PĀ <Ā 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 (PĀ =Ā 0.052); Furthermore, the TP53 mutation rate increased as MATH was elevated (PĀ <Ā 0.001), whereas CDH1 mutations were correlated with a lower level of MATH (PĀ =Ā 0.002). Several focal and arm-level SCNA events were more common in the high MATH group (PĀ <Ā 0.05), including Chr8q24 with only the MYC gene in the āpeakā region. Similarly, high MATH was associated with gene set enrichment related to the MYC pathway and proliferation. 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.
datePublished:2017-01-16T00:00:00Z
dateModified:2017-01-16T00:00:00Z
pageStart:39
pageEnd:48
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Intra-tumor genetic heterogeneity
Mutant-allele tumor heterogeneity
The Cancer Genome Atlas
Breast cancer
MYC
Oncology
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headline:Clinical and molecular relevance of mutant-allele tumor heterogeneity in breast cancer
description: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. 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. 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 PĀ <Ā 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 (PĀ =Ā 0.052); Furthermore, the TP53 mutation rate increased as MATH was elevated (PĀ <Ā 0.001), whereas CDH1 mutations were correlated with a lower level of MATH (PĀ =Ā 0.002). Several focal and arm-level SCNA events were more common in the high MATH group (PĀ <Ā 0.05), including Chr8q24 with only the MYC gene in the āpeakā region. Similarly, high MATH was associated with gene set enrichment related to the MYC pathway and proliferation. 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.
datePublished:2017-01-16T00:00:00Z
dateModified:2017-01-16T00:00:00Z
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Intra-tumor genetic heterogeneity
Mutant-allele tumor heterogeneity
The Cancer Genome Atlas
Breast cancer
MYC
Oncology
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