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Truncating mutations of RB1CC1 in human breast cancer

Nature Genetics volume 31, pages 285–288 (2002)Cite this article

Abstract

The protein RB1CC1 (retinoblastoma 1 (RB1)-inducible coiled-coil 1) has been identified as a key regulator of the tumor-suppressor gene RB1 (ref. 1). RB1CC1 is localized in the nucleus and has been proposed to be a transcription factor because of its nuclear localization signal, leucine zipper motif and coiled-coil structure1,2. The gene RB1CC1 is localized to a region of chromosome 8q11 (ref. 2) containing several loci of putative tumor-suppressor genes3,4; however, its role in human cancers remains to be determined. Here we report that 20% (7 of 35) of primary breast cancers examined contained mutations in RB1CC1, including nine large interstitial deletions predicted to yield markedly truncated RB1CC1 proteins. Wildtype RB1CC1 and RB1 were absent or significantly less abundant than normal in the seven cancers with mutations in RB1CC1, but were abundant in cancers without such mutations. In all seven cancers, both RB1CC1 alleles were inactivated; two showed compound heterozygous deletions. Thus, RB1CC1 is frequently mutated in breast cancer and shows characteristics of a classical tumor-suppressor gene.

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Figure 1: Loss of heterozygosity at the RB1CC1 locus (D8S567) in primary breast cancers.
Figure 2: Location and predicted outcome of RB1CC1 mutations.
Figure 3: Mutation analysis of RB1CC1.
Figure 4: Immunohistochemical analysis of RB1CC1 and RB1 in MMK3, 6 and 12.

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Acknowledgements

We thank A. Mabuchi for computational searches and H. Honjo, H. Chen, N. Takashima, M. Sugimoto, K. Kobayashi and J. Shimizu for experimental assistance. This study was partially supported by grant-in-aids for Japan Society for the Promotion of Science Fellows, Scientific Research (B), The Ministry of Education, Science, Sports and Culture of Japan, and a grant from the Japan Orthopaedics and Traumatology Foundation.

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Authors and Affiliations

  1. Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Seta, Otsu, 520-2192, Shiga, Japan

    Tokuhiro Chano & Hidetoshi Okabe

  2. Department of Surgery II, Shiga University of Medical Science, Seta, Otsu, 520-2192, Shiga, Japan

    Keiichi Kontani & Koji Teramoto

  3. Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN,, Tokyo, 108-8639, Japan

    Shiro Ikegawa

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  1. Tokuhiro Chano
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Correspondence to Tokuhiro Chano.

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Chano, T., Kontani, K., Teramoto, K. et al. Truncating mutations of RB1CC1 in human breast cancer. Nat Genet 31, 285–288 (2002). https://doi.org/10.1038/ng911

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