2014年3月21日金曜日

R-spondinと癌の続報は「さっぱり」である

R-spondinと癌の続報であるが、これが全く出てこないのである。約一年半になるが、なしのつぶて。これはさすがに怪しい。当初は10%に認めるといっておきながら、誰も追試できない(R-Spondinそのものは腸管stem cell等々でなかなかお盛んな遺伝子なので、興味をひいた研究者は多かったはずなのだが)。がっかりである。natureで追試できない一例であろう、おそらくね。

Nature (2012)

Received
Accepted
Published online

Recurrent R-spondin fusions in colon cancer

Department of Molecular Biology, Genentech Inc

Somasekar Seshagiri, Eric W. Stawiski, Steffen Durinck, Zora Modrusan, Elaine E. Storm, Caitlin B. Conboy, Subhra Chaudhuri, Yinghui Guan, Vasantharajan Janakiraman, Bijay S. Jaiswal, Joseph Guillory, Connie Ha, Gerrit J. P. Dijkgraaf, Jeremy Stinson, Florian Gnad, Melanie A. Huntley, Jeremiah D. Degenhardt, Peter M. Haverty, Richard Bourgon, Weiru Wang, Hartmut, Koeppen, Robert Gentleman, Timothy K. Starr, Zemin Zhang, David A. Largaespada, Thomas D. Wu & Frederic J. de Sauvage

  • Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics1. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.

1 件のコメント:

匿名 さんのコメント...

いつも楽しく読ませていただいております。前駆病変におけるRSPO融合が報告されました。
J Pathol. 2016
Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma.