Analysis of the transcription regulator, CNOT7, as a candidate chromosome 8 tumor suppressor gene in colorectal cancer.
Loss of heterozygosity (LOH) on the short arm of chromosome 8 occurs at high frequencies in many tumor types, including colorectal carcinoma. We have previously used microcell-mediated chromosome transfer (MMCT) to map an approximately 7.7 Mb colorectal cancer suppressor region (CRCSR) at 8p22-23.1. We have now taken a candidate gene approach to identify the putative tumor suppressor gene located within the CRCSR. CNOT7 encodes a subunit of the CCR4-Not transcription complex and is located at 8p22. We showed that CNOT7 is expressed in normal colonic mucosa and in colonic crypt cells, as well as in colorectal cell lines and primary tumors. We assembled a panel of 88 primary colorectal tumors comprising 20 MSI-high (high microsatellite instability), 19 MSI-low and 49 MSS (microsatellite stable) tumors for mutation analysis of the CNOT7 gene. Denaturing high-performance liquid chromatography (DHPLC) analysis of the entire coding region of the CNOT7 gene revealed only one somatic missense mutation in an MSS tumor. The rarity of somatic mutations in CNOT7, and its expression in primary colorectal tumors and cell lines, suggests that CNOT7 is not the target tumor suppressor gene in the 8p22-23.1 CRCSR.
Flanagan
James
J
The Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland, Australia.
Healey
Sue
S
The Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland, Australia.
Young
Joanne
J
Royal Brisbane Hospital Department of Pathology, Herston, Queensland, Australia.
Whitehall
Vicki
V
The Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland, Australia.
Chenevix-Trench
Georgia
G
The Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland, Australia.
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D056504:Chromatin Assembly Factor-1; D002851:Chromatography, High Pressure Liquid; D002868:Chromosomal Proteins, Non-Histone; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm