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

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 +18 more·2010·Genome Research

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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  • Over the last two years, Illumina transcriptome or whole genome de novo sequencing and assembly have been successfully used for model and non-model organisms.

    “Over the last two years, with the further confirmation that the relatively short reads can be effectively assembled [15], especially with the great advantage of paired-end sequencing [54], the Illumina transcriptome or whole genome de novo sequencing and assembly have been successfully used for model [12,16,55-58]and non-model organisms [25-27,59].”

    From De novo assembly and characterization of root transcriptome using Illumina paired-end sequencing and development of cSSR markers in sweetpotato (Ipomoea batatas) (2010) · cites this paper as [56]

    The Discussion reports successful Illumina paired-end transcriptome sequencing of human melanoma samples, supporting this paper as an example of sequencing in a model organism. But the 'Alignment of reads to the transcriptome and genome' section says reads were aligned to existing human transcriptome and genome references; it does not support the claim of de novo assembly. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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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)
Venue
Genome Research
Published
2010-02-23
Volume
20
Issue
4
Pages
413-427
ISSN
1088-9051 (ISSN-L)
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
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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