title: Truncating mutations of RB1CC1 in human breast cancer.
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 structure. The gene RB1CC1 is localized to a region of chromosome 8q11 (ref. 2) containing several loci of putative tumor-suppressor genes; 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.
authors.affiliation: Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan. chano@belle.shiga-med.ac.jp
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Chano
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kontani
authors.forename: Koji
authors.initials: K
authors.lastname: Teramoto
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okabe
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000071183:Autophagy-Related Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D016153:Genes, Suppressor; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation / Q000235:genetics*; D011505:Protein-Tyrosine Kinases; D016160:Retinoblastoma Protein / Q000235:genetics*
chemical_list: D000071183:Autophagy-Related Proteins; D005819:Genetic Markers; C407704:RB1CC1 protein, human; D016160:Retinoblastoma Protein; D004247:DNA; D011505:Protein-Tyrosine Kinases