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Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma.

Publication ,  Journal Article
Palanisamy, N; Ateeq, B; Kalyana-Sundaram, S; Pflueger, D; Ramnarayanan, K; Shankar, S; Han, B; Cao, Q; Cao, X; Suleman, K; Kumar-Sinha, C ...
Published in: Nat Med
July 2010

Although recurrent gene fusions involving erythroblastosis virus E26 transformation-specific (ETS) family transcription factors are common in prostate cancer, their products are considered 'undruggable' by conventional approaches. Recently, rare targetable gene fusions involving the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, have been identified in 1-5% of lung cancers, suggesting that similar rare gene fusions may occur in other common epithelial cancers, including prostate cancer. Here we used paired-end transcriptome sequencing to screen ETS rearrangement-negative prostate cancers for targetable gene fusions and identified the SLC45A3-BRAF (solute carrier family 45, member 3-v-raf murine sarcoma viral oncogene homolog B1) and ESRP1-RAF1 (epithelial splicing regulatory protein-1-v-raf-1 murine leukemia viral oncogene homolog-1) gene fusions. Expression of SLC45A3-BRAF or ESRP1-RAF1 in prostate cells induced a neoplastic phenotype that was sensitive to RAF and mitogen-activated protein kinase kinase (MAP2K1) inhibitors. Screening a large cohort of patients, we found that, although rare, recurrent rearrangements in the RAF pathway tend to occur in advanced prostate cancers, gastric cancers and melanoma. Taken together, our results emphasize the key role of RAF family gene rearrangements in cancer, suggest that RAF and MEK inhibitors may be useful in a subset of gene fusion-harboring solid tumors and demonstrate that sequencing of tumor transcriptomes and genomes may lead to the identification of rare targetable fusions across cancer types.

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Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

July 2010

Volume

16

Issue

7

Start / End Page

793 / 798

Location

United States

Related Subject Headings

  • Translocation, Genetic
  • Stomach Neoplasms
  • Signal Transduction
  • RNA-Binding Proteins
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins B-raf
  • Prostatic Neoplasms
  • Oncogene Proteins, Fusion
  • Monosaccharide Transport Proteins
  • Membrane Transport Proteins
 

Citation

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MLA
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Palanisamy, N., Ateeq, B., Kalyana-Sundaram, S., Pflueger, D., Ramnarayanan, K., Shankar, S., … Chinnaiyan, A. M. (2010). Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat Med, 16(7), 793–798. https://doi.org/10.1038/nm.2166
Palanisamy, Nallasivam, Bushra Ateeq, Shanker Kalyana-Sundaram, Dorothee Pflueger, Kalpana Ramnarayanan, Sunita Shankar, Bo Han, et al. “Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma.Nat Med 16, no. 7 (July 2010): 793–98. https://doi.org/10.1038/nm.2166.
Palanisamy N, Ateeq B, Kalyana-Sundaram S, Pflueger D, Ramnarayanan K, Shankar S, et al. Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat Med. 2010 Jul;16(7):793–8.
Palanisamy, Nallasivam, et al. “Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma.Nat Med, vol. 16, no. 7, July 2010, pp. 793–98. Pubmed, doi:10.1038/nm.2166.
Palanisamy N, Ateeq B, Kalyana-Sundaram S, Pflueger D, Ramnarayanan K, Shankar S, Han B, Cao Q, Cao X, Suleman K, Kumar-Sinha C, Dhanasekaran SM, Chen Y-B, Esgueva R, Banerjee S, LaFargue CJ, Siddiqui J, Demichelis F, Moeller P, Bismar TA, Kuefer R, Fullen DR, Johnson TM, Greenson JK, Giordano TJ, Tan P, Tomlins SA, Varambally S, Rubin MA, Maher CA, Chinnaiyan AM. Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat Med. 2010 Jul;16(7):793–798.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

July 2010

Volume

16

Issue

7

Start / End Page

793 / 798

Location

United States

Related Subject Headings

  • Translocation, Genetic
  • Stomach Neoplasms
  • Signal Transduction
  • RNA-Binding Proteins
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins B-raf
  • Prostatic Neoplasms
  • Oncogene Proteins, Fusion
  • Monosaccharide Transport Proteins
  • Membrane Transport Proteins