OBJECTIVES: To test whether genetic instability may determine whether tumours become aneuploid or diploid. MATERIALS AND METHODS: We have identified genes needed for cell survival or replication by combining Affymetrix gene expression array data from 12 experimental cell lines with in silico GEO+GNF and expO databases. Specific loss of heterozygosis (LOHs), chromosomal abnormalities (called derivative chromosomes) and numbers of normal homologues were identified by SNP and SKY analyses. Random gene losses were calculated under the assumption that bi-allelic MMR gene inactivation causes a 20-fold increase in rate of gene loss. RESULTS: There were ∼1.23 × 10(4) genes widely dispersed throughout the genome and possibly expressed by all cells for survival or proliferation, many of these genes performed housekeeping functions. Conservation of the genes may explain the complete haploid genomes found for 15 different cell types and derivative chromosomes selectively retained in aneuploid cancer cell lines after LOH formations, and normal homologue losses. Loss of cell survival/replication genes was calculated to be higher in colon stem cells of carriers of MMR gene mutations than carriers of APC gene mutations. CONCLUSION: Random loss of cell survival/replication genes was calculated to be low enough for colon stem cells with APC gene mutations to 'select' LOH and derivative chromosome combinations favouring tumour cell proliferation. However, cell survival/replication gene loss was calculated to be too high for colonic stem cells lacking MMR genes to survive chromosomal instability, explaining why MMR mutations only produce tumours with diploid chromosome cells.
OBJECTIVES: To test whether genetic instability may determine whether tumours become aneuploid or diploid. MATERIALS AND METHODS: We have identified genes needed for cell survival or replication by combining Affymetrix gene expression array data from 12 experimental cell lines with in silico GEO+GNF and expO databases. Specific loss of heterozygosis (LOHs), chromosomal abnormalities (called derivative chromosomes) and numbers of normal homologues were identified by SNP and SKY analyses. Random gene losses were calculated under the assumption that bi-allelic MMR gene inactivation causes a 20-fold increase in rate of gene loss. RESULTS: There were ∼1.23 × 10(4) genes widely dispersed throughout the genome and possibly expressed by all cells for survival or proliferation, many of these genes performed housekeeping functions. Conservation of the genes may explain the complete haploid genomes found for 15 different cell types and derivative chromosomes selectively retained in aneuploid cancer cell lines after LOH formations, and normal homologue losses. Loss of cell survival/replication genes was calculated to be higher in colon stem cells of carriers of MMR gene mutations than carriers of APC gene mutations. CONCLUSION: Random loss of cell survival/replication genes was calculated to be low enough for colon stem cells with APC gene mutations to 'select' LOH and derivative chromosome combinations favouring tumour cell proliferation. However, cell survival/replication gene loss was calculated to be too high for colonic stem cells lacking MMR genes to survive chromosomal instability, explaining why MMR mutations only produce tumours with diploid chromosome cells.
Authors: T Sugai; W Habano; S Nakamura; H Sato; N Uesugi; H Takahashi; Y Jiao; T Yoshida; C Itoh Journal: Int J Cancer Date: 2000-11-15 Impact factor: 7.396
Authors: Christopher Greenman; Philip Stephens; Raffaella Smith; Gillian L Dalgliesh; Christopher Hunter; Graham Bignell; Helen Davies; Jon Teague; Adam Butler; Claire Stevens; Sarah Edkins; Sarah O'Meara; Imre Vastrik; Esther E Schmidt; Tim Avis; Syd Barthorpe; Gurpreet Bhamra; Gemma Buck; Bhudipa Choudhury; Jody Clements; Jennifer Cole; Ed Dicks; Simon Forbes; Kris Gray; Kelly Halliday; Rachel Harrison; Katy Hills; Jon Hinton; Andy Jenkinson; David Jones; Andy Menzies; Tatiana Mironenko; Janet Perry; Keiran Raine; Dave Richardson; Rebecca Shepherd; Alexandra Small; Calli Tofts; Jennifer Varian; Tony Webb; Sofie West; Sara Widaa; Andy Yates; Daniel P Cahill; David N Louis; Peter Goldstraw; Andrew G Nicholson; Francis Brasseur; Leendert Looijenga; Barbara L Weber; Yoke-Eng Chiew; Anna DeFazio; Mel F Greaves; Anthony R Green; Peter Campbell; Ewan Birney; Douglas F Easton; Georgia Chenevix-Trench; Min-Han Tan; Sok Kean Khoo; Bin Tean Teh; Siu Tsan Yuen; Suet Yi Leung; Richard Wooster; P Andrew Futreal; Michael R Stratton Journal: Nature Date: 2007-03-08 Impact factor: 49.962
Authors: Scott L Carter; Kristian Cibulskis; Elena Helman; Aaron McKenna; Hui Shen; Travis Zack; Peter W Laird; Robert C Onofrio; Wendy Winckler; Barbara A Weir; Rameen Beroukhim; David Pellman; Douglas A Levine; Eric S Lander; Matthew Meyerson; Gad Getz Journal: Nat Biotechnol Date: 2012-05 Impact factor: 54.908
Authors: David A Weaver; Andrea L Nestor-Kalinoski; Kristen Craig; Matthew Gorris; Tejal Parikh; Helen Mabry; David C Allison Journal: Genes Chromosomes Cancer Date: 2013-11-30 Impact factor: 5.006