Dataset Information

Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling.

ABSTRACT:

Introduction

Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Those ATC with genomic alterations (GAs) in TSC2, ALK, and BRAF may respond to targeted therapies.

Methods

Comprehensive genomic profiling on 90 ATC specimens identified base substitutions, short insertions and deletions, amplifications, copy number alterations, and genomic rearrangements in up to 315 cancer-related genes and 28 genes commonly rearranged in cancer.

Results

Median patient age was 65 (range, 33-86) years, 50 patients were male. There was a mean of 4.2 GA per case, range 1-11. The most common GA were TP53 (66%), BRAF (34%), TERT (32%), CDKN2A (32%), and NRAS (26%). BRAF V600E and NRAS/HRAS/KRAS alteration were mutually exclusive. BRAF, CDKN2A, PIK3CA, and JAK2 were more frequent in patients >70 years of age; while myc, PTEN, and NRAS were more common in those ≤50 years.

Conclusion

ATC shows many GA with potential therapeutic significance and suggesting different molecular pathways can lead to ATC.

SUBMITTER: Khan SA

PROVIDER: S-EPMC6542589 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling.

Khan Saad A SA Ci Bo B Xie Yang Y Gerber David E DE Beg Muhammad S MS Sherman Steven I SI Cabanillas Maria E ME Busaidy Naifa L NL Burtness Barbara A BA Heilmann Andreas M AM Bailey Mark M Ross Jeffrey S JS Sher David J DJ Ali Siraj M SM

Head & neck 20190213 6

<h4>Introduction</h4>Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Those ATC with genomic alterations (GAs) in TSC2, ALK, and BRAF may respond to targeted therapies.<h4>Methods</h4>Comprehensive genomic profiling on 90 ATC specimens identified base substitutions, short insertions and deletions, amplifications, copy number alterations, and genomic rearrangements in up to 315 cancer-related genes and 28 genes commonly rearranged in cancer.<h4>Results</h4>Median patient age ...[more]

PMID: 30758123

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Project description:BackgroundGermline mutations in numerous genes, particularly tumor suppressor genes, markedly heighten the risk of various cancers, including lung cancer, which is the leading cause of cancer-related deaths worldwide. Despite extensive research on well-known genes like BRCA1, BRCA2, and mismatch repair genes, many genetic factors contributing to cancer susceptibility remain unidentified.MethodsThis study reviewed sequencing data from 4,934 Chinese lung cancer patients. Matched white blood cell samples were sequenced using WES or gene panels to identify germline mutations. Analysis included statistical tests to compare patient demographics, clinical characteristics, and somatic mutation profiles.ResultsAmong the cohort, 89 patients carried pathogenic/likely pathogenic (P/LP) germline mutations in 20 known cancer susceptibility genes, with ATM, BRCA2, and CHEK2 being the most common. TP53 mutations were linked to early-onset lung cancer, while ATM mutations correlated with late-onset and higher PD-L1 expression, suggesting immunotherapy benefits. Germline mutations were more prevalent in younger patients and females. Somatic mutation profiles showed similarities in common mutations but differences in MTOR (p = 0.044) and MSH6 (p = 0.018) mutations in P/LP carriers. GO and KEGG analyses indicated distinct biological processes and pathways in patients with P/LP germline mutations. Gene exclusivity analysis revealed correlations and mutual exclusivity between specific germline and somatic mutations. Comparative analysis with the gnomAD database showed a higher prevalence of these mutations in lung cancer patients compared to the general and East Asian populations, suggesting an association with increased lung cancer risk in the Chinese cohort.ConclusionThis study underscores the prevalence of germline mutations in Chinese lung cancer patients, identifying significant associations with clinical characteristics and somatic mutation profiles. The findings highlight the importance of considering germline mutations in lung cancer treatment and the potential benefits of personalized therapy based on genetic susceptibility.

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Dataset Information

Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling.

Introduction

Methods

Results

Conclusion

Publications

Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling.

Similar Datasets

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