Dear all,
I have been reading a review article published on Nature Review Clinical Oncology in 2013. In the paper entitled "Mutational landscape of HCC", I noticed that TTN was labeled as a gene frequently mutated in HCC in Table 1 but I couldn't find reference for it in the article and PubMed. Does anyone know where the citation is? I have emailed both authors months ago, but no responses.
Especially, I would love to know TTN mutation' roles in chromosome segregation.
Villanueva, A. & Llovet, J. M. Nat. Rev. Clin. Oncol. 11, 73–74 (2014); published online 7 January 2014; doi:10.1038/nrclinonc.2013.243
http://www.ncbi.nlm.nih.gov/pubmed/24395088
I don't know about any papers discussing TTN mutations in HCC, but having been involved in various NextGen sequencing projects I can tell you that TTN is often mutated in many cancers just because it is an enormous gene (313 exons, 34350 amino acids and 3816030 Da). Hence its name. I would be difficult to accrue any biological evidence that mutations in TTN are actually related to tumourigensis or tumour maintenance. Likely they are just passenger mutations.
Large genes (>4000aa), genes that span large loci (>1Mb), genes that have low expression levels, tend to have higher mutation rates but might not actually be associated with cancer. Other examples are several mucin genes and olfactory receptors genes which appear on many mutation analyses. ( see http://www.nature.com/nature/journal/v499/n7457/full/nature12213.html )
Pawel is correct. You may also take a look also at these papers: Nature. 2013;499(7457):214-8 and at the SI of PLoS Genet. 2013;9(9):e1003816. However, if you are interested, the list of mutations should be available from TCGA, the Sanger Institute and the ICGC.
@Pawel: Thanks for reply! Yes, I am aware of the titanic TTN and MutSigCV paper. Some papers even excludes TTN mutations right before any analysis. But, there are many muscular disorders resulted from TTN mutations. It is not entirely impossible that TTN mutations are not significant. Also, the review paper showed that the mutated rate of TTN in HCC is about 4 -10%. It conflicts with the idea that somatic mutations of TTN is frequently seen. I mean, the assumption of MutSigCV's paper is indeed charming. I love it. But, it doesn't mean that mutated TTN has no chance to contribute in tumorigenesis. It is indeed very difficult to validate mutations on TTN because of its size. It is indeed that TTN is low abundant and may not have detectable expression levels (RNA and protein). Then, where did the citation of the review paper comes from? By the way, IntOGen considers somatic mutations in TTN as "driver mutation" in lung and bronchus cancer data from TCGA.
http://www.intogen.org/web/mutations/v04/search?4
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