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Reassessing the TARBP2 mutation rate in hereditary nonpolyposis colorectal cancer

Nature Genetics volume 42, pages 817–818 (2010)Cite this article

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To the Editor:

Recently, Melo et al.1 proposed that somatic mutations targeting the microRNA (miRNA)-processing machinery play an important role in human tumorigenesis. Supporting their view, they detected truncating mutations in TARBP2 (encoding TAR RNA-binding protein 2) in microsatellite-instable (MSI) tumors1. MSI tumors have a DNA mismatch repair deficiency causing the accumulation of insertion and/or deletion mutations at short repetitive sequences2. It is therefore not surprising that TARBP2 mutations target coding repeat sequences. More specifically, Melo et al.1 described two mutations: a C deletion in a (C)5 repeat and a C insertion in a (C)7 repeat, both located in exon 5 (ref. 1). The presence of inactivating mutations in TARBP2 enhances cellular transformation and leads to a secondary defect in DICER1(ref. 1), a TARBP2-interacting double-stranded RNA-specific endoRNase that processes pre-miRNAs into miRNAs3. The authors report the incidence of TARBP2 frameshift mutations in human primary MSI tumors, finding higher mutation rates in hereditary non-polyposis colorectal cancers (HNPCC) (13 out of 30) than in sporadic colorectal (53 out of 209) or gastric (6 out of 43) cancers1. Mutations were not detected in microsatellite-stable colorectal cancers (0 out of 50), normal colon (0 out of 50) or lymphocytes from individuals with HNPCC1 (0 out of 12). Taken together, it appears that TARBP2 is a new bona fide MSI target gene (that is, a gene with coding repeat sequences accumulating insertion and/or deletion mutations under positive selection during cancer progression).

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Acknowledgements

The present study was supported by Instituto de Salud Carlos III (ISCIII) research grants RD06/0020/0021, FIS07/0359 and FIS09/00859 from the Spanish Ministry of Science and Innovation.

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Authors and Affiliations

  1. Laboratorio de Oncología Molecular, Hospital Clínico San Carlos, Madrid, Spain

    Pilar Garre & Miguel de la Hoya

  2. Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, Spain

    Pedro Pérez-Segura, Eduardo Díaz-Rubio & Trinidad Caldés

Authors
  1. Pilar Garre
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  2. Pedro Pérez-Segura
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  3. Eduardo Díaz-Rubio
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  4. Trinidad Caldés
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  5. Miguel de la Hoya
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Contributions

Experiments were designed by M.d.l.H. Experiments were performed and overseen by P.G., T.C. and M.d.l.H. Data was analyzed by P.G., T.C. and M.d.l.H. Clinical and molecular characterization of MSI-HNPCC tumors was performed by P.P.-S., E.D.-R. and T.C. The manuscript was written by M.d.l.H and P.G., with input from all other authors.

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Correspondence to Miguel de la Hoya.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Figures 1 and 2 and Supplementary Table 1 (PDF 382 kb)

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Garre, P., Pérez-Segura, P., Díaz-Rubio, E. et al. Reassessing the TARBP2 mutation rate in hereditary nonpolyposis colorectal cancer. Nat Genet 42, 817–818 (2010). https://doi.org/10.1038/ng1010-817

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