title: Characterizing the prevalence of chromosome instability in interval colorectal cancer.
abstract: A substantial proportion of colorectal cancers (CRCs) are interval CRCs (I-CRCs; i.e., CRCs diagnosed soon after a colonoscopy). Chromosomal instability (CIN) is defined as an increase in the rate of which whole chromosomes/large chromosomal fragments are gained or lost and is observed in 85% of non-hereditary CRCs. The contribution of CIN to the etiology of I-CRCs remains unknown. We established a fluorescence in situ hybridization (FISH) approach to characterize CIN by enumerating specific chromosomes and determined the prevalence of numerical CIN in a population-based cohort of I-CRCs and control (sporadic) CRCs. Using the population-based Manitoba Health administrative databases and Manitoba Cancer Registry, we identified an age, sex, and colonic site of CRC matched cohort of I-CRCs and controls and retrieved their archived paraffin-embedded tumor samples. FISH chromosome enumeration probes specifically recognizing the pericentric regions of chromosomes 8, 11, and 17 were first used on cell lines and then CRC tissue microarrays to detect aneusomy, which was then used to calculate a CIN score (CS). The 15th percentile CS for control CRC was used to define CIN phenotype. Mean CSs were similar in the control CRCs and I-CRCs; 82% of I-CRCs exhibited a CIN phenotype, which was similar to that in the control CRCs. This study suggests that CIN is the most prevalent contributor to genomic instability in I-CRCs. Further studies should evaluate CIN and microsatellite instability (MSI) in the same cohort of I-CRCs to corroborate our findings and to further assess concomitant contribution of CIN and MSI to I-CRCs.
authors: University of Manitoba, Winnipeg, Canada; Department of Biochemistry and Medical Genetics, Winnipeg, Canada; Research Institute of Oncology and Hematology, Winnipeg, Canada.
authors: A L
authors: AL
authors: Cisyk
authors: University of Manitoba, Winnipeg, Canada; Department of Biochemistry and Medical Genetics, Winnipeg, Canada; Research Institute of Oncology and Hematology, Winnipeg, Canada.
authors: S
authors: S
authors: Penner-Goeke
authors: University of Manitoba, Winnipeg, Canada; Department of Biochemistry and Medical Genetics, Winnipeg, Canada; Research Institute of Oncology and Hematology, Winnipeg, Canada.
authors: Z
authors: Z
authors: Lichtensztejn
authors: CancerCare Manitoba, Winnipeg, Canada.
authors: Z
authors: Z
authors: Nugent
authors: University of Manitoba, Winnipeg, Canada; Department of Pathology, Winnipeg, Canada; Grace Hospital, Winnipeg, Canada.
authors: R H
authors: RH
authors: Wightman
authors: University of Manitoba, Winnipeg, Canada; Department of Internal Medicine, Health Sciences Centre, Winnipeg, Canada.
authors: H
authors: H
authors: Singh
authors: University of Manitoba, Winnipeg, Canada; Department of Biochemistry and Medical Genetics, Winnipeg, Canada; Research Institute of Oncology and Hematology, Winnipeg, Canada. Electronic address: Kirk.McManus@med.umanitoba.ca.
authors: K J
authors: KJ
authors: McManus
mesh_terms: D000367:Age Factors; D000368:Aged; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015995:Prevalence; D012680:Sensitivity and Specificity; D012737:Sex Factors