Cited by 309Cancer Genomics and DiagnosticsCutaneous Melanoma Detection and ManagementGenomics and Phylogenetic Studies

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Integrative analysis of the melanoma transcriptome

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Berger, Michael F., Levin, Joshua Z., Vijayendran, Krishna, Sivachenko, Andrey, Adiconis, Xian, Maguire, Jared, Johnson, Laura A., Robinson, James, Verhaak, Roel G., Sougnez, Carrie, Onofrio, Robert C., Ziaugra, Liuda, Cibulskis, Kristian, Laine, Elisabeth, Barretina, Jordi, Winckler, Wendy, Fisher, David E., Getz, Gad, Meyerson, Matthew, Jaffe, David B., Gabriel, Stacey B., Lander, Eric S., Dummer, Reinhard, Gnirke, Andreas, Nusbaum, Chad, Garraway, Levi A.·2010·Genome Research

DOI 10.1101/gr.103697.109PMC PMC2847744

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Abstract

Global studies of transcript structure and abundance in cancer cells enable the systematic discovery of aberrations that contribute to carcinogenesis, including gene fusions, alternative splice isoforms, and somatic mutations. We developed a systematic approach to characterize the spectrum of cancer-associated mRNA alterations through integration of transcriptomic and structural genomic data, and we applied this approach to generate new insights into melanoma biology. Using paired-end massively parallel sequencing of cDNA (RNA-seq) together with analyses of high-resolution chromosomal copy number data, we identified 11 novel melanoma gene fusions produced by underlying genomic rearrangements, as well as 12 novel readthrough transcripts. We mapped these chimeric transcripts to base-pair resolution and traced them to their genomic origins using matched chromosomal copy number information. We also used these data to discover and validate base-pair mutations that accumulated in these melanomas, revealing a surprisingly high rate of somatic mutation and lending support to the notion that point mutations constitute the major driver of melanoma progression. Taken together, these results may indicate new avenues for target discovery in melanoma, while also providing a template for large-scale transcriptome studies across many tumor types.

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Additional file 2 of Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
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Additional file 4 of Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
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Additional file 5 of De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweetpotato (Ipomoea batatas)
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Additional file 6 of De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweetpotato (Ipomoea batatas)
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Additional file 1 of Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
Parisi, F., Ariyan, S., Narayan, D., Bacchiocchi, A., Hoyt, K., Cheng, E., Xu, F., Li, P., Halaban, R., & Kluger, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12875583
Additional file 5 of Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
Parisi, F., Ariyan, S., Narayan, D., Bacchiocchi, A., Hoyt, K., Cheng, E., Xu, F., Li, P., Halaban, R., & Kluger, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12875595
Additional file 3 of De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweetpotato (Ipomoea batatas)
Wang, Z., Fang, B., Chen, J., Zhang, X., Luo, Z., Huang, L., Chen, X., & Li, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12880610
Additional file 8 of De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweetpotato (Ipomoea batatas)
Wang, Z., Fang, B., Chen, J., Zhang, X., Luo, Z., Huang, L., Chen, X., & Li, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12880625
Additional file 7 of Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
Parisi, F., Ariyan, S., Narayan, D., Bacchiocchi, A., Hoyt, K., Cheng, E., Xu, F., Li, P., Halaban, R., & Kluger, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12875601
Additional file of Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
Parisi, F., Ariyan, S., Narayan, D., Bacchiocchi, A., Hoyt, K., Cheng, E., Xu, F., Li, P., Halaban, R., & Kluger, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12875604
Additional file 1 of SMOOTH-seq: single-cell genome sequencing of human cells on a third-generation sequencing platform
Fan, X., Yang, C., Li, W., Bai, X., Zhou, X., Xie, H., Wen, L., & Tang, F. (2021) · Figshare · doi:10.6084/m9.figshare.14889777
Additional file 6 of Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
Parisi, F., Ariyan, S., Narayan, D., Bacchiocchi, A., Hoyt, K., Cheng, E., Xu, F., Li, P., Halaban, R., & Kluger, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12875598
Additional file 11 of De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweetpotato (Ipomoea batatas)
Wang, Z., Fang, B., Chen, J., Zhang, X., Luo, Z., Huang, L., Chen, X., & Li, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12880601
Additional file of De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweetpotato (Ipomoea batatas)
Wang, Z., Fang, B., Chen, J., Zhang, X., Luo, Z., Huang, L., Chen, X., & Li, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12880631
Additional file 9 of De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweetpotato (Ipomoea batatas)
Wang, Z., Fang, B., Chen, J., Zhang, X., Luo, Z., Huang, L., Chen, X., & Li, Y. (2020) · Figshare · doi:10.6084/m9.figshare.12880628

Authors: Berger, M. F., Levin, J. Z., Vijayendran, K., Sivachenko, A., Adiconis, X., Maguire, J., Johnson, L. A., Robinson, J., Verhaak, R. G., Sougnez, C., Onofrio, R. C., Ziaugra, L., Cibulskis, K., Laine, E., Barretina, J., Winckler, W., Fisher, D. E., Getz, G., Meyerson, M., Jaffe, D. B., Gabriel, S. B., Lander, E. S., Dummer, R., Gnirke, A., Nusbaum, C., & Garraway, L. A.
Affiliations: Broad Institute (US)
University Hospital Zurich (CH)
Boston Children's Hospital (US)
ORCID: Levin, Joshua Z.
Sivachenko, Andrey
Verhaak, Roel G.
Cibulskis, Kristian
Barretina, Jordi
Winckler, Wendy
Fisher, David E.
Getz, Gad
Meyerson, Matthew
Jaffe, David B.
Gabriel, Stacey B.
Dummer, Reinhard
Gnirke, Andreas
Nusbaum, Chad
Garraway, Levi A.
Venue: Genome Research
Publisher: Cold Spring Harbor Laboratory
Published: 2010-02-23
Volume: 20
Issue: 4
Pages: 413-427
ISSN: 1088-9051 (ISSN-L)
DOI: 10.1101/gr.103697.109
PMC: PMC2847744
OpenAlex: W6948519597
Cited by: 305
References: 66
Citations by year: 2026: 1 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 11 · 2020: 25 · 2019: 11 · 2018: 17 · 2017: 25 · 2016: 22 · 2015: 14 · 2014: 21 · 2013: 35 · 2012: 52
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genome Research (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
HighWire Press Open Archive (submittedVersion)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Zurich Open Repository and Archive (University of Zurich)
Funders: Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
Broad Institute
National Human Genome Research Institute (U54HG003067)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR043369)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords: melanoma, transcriptome, gene fusion, read-through transcripts, fusion transcripts, somatic mutations, chromosomal copy number alterations, alternative splicing, transcriptome integration, structural genomics, carcinogenesis, point mutations
MeSH terms: Base Sequence, DNA Mutational Analysis, Gene Amplification, Humans, Melanoma, Polymorphism, Genetic, Skin Neoplasms, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Matched-Pair Analysis, Sequence Analysis, DNA, Systems Integration, Gene Dosage, K562 Cells, Protein Isoforms, Gene Expression Profiling, Genomics, Gene Fusion

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