Role of short telomeres in inducing preferential chromosomal aberrations in human ovarian surface epithelial cells: A combined telomere quantitative fluorescence in situ hybridization and whole-chromosome painting study.
It is well established that specific cancers and immortalized cells have nonrandom chromosome aberrations. However, little is understood about the underlying mechanism that initiates these aberrations in human cells. To examine whether human chromosomes with the shortest telomeres initiate the preferential chromosomal aberrations before cellular immortalization, we simultaneously applied telomere quantitative fluorescence in situ hybridization and specific whole-chromosome painting on chromosomes 1, 5, 8, 17, 19, and 20 in human ovarian surface epithelial (HOSE 6-3) cells expressing human papilloma viral oncogenes (HPV16 E6E7). The HPV16 E6E7-expressing cells, with extended in vitro life span and telomerase-negative status, were previously identified as having nonrandom chromosomal imbalances and high frequencies of dicentrics. Our analyses showed that among six pairs of targeted chromosomes, chromosomes 8 and 20 showed critically short telomeres with an undetectable telomere signal in more than 50% of cells analyzed. These chromosomes with the critically short telomeres were preferentially involved in various types of chromosomal aberrations including dicentrics, translocations, breaks, insertions, and losses or gains of chromosomal elements. Our findings suggest that nonrandom chromosome aberrations in HOSE cells occurring before cellular immortalization could be caused by the telomere length heterogeneity.
Deng
Wen
W
Department of Anatomy, The University of Hong Kong, Hong Kong, SAR, China.
Tsao
Sai Wah
SW
Guan
Xin-Yuan
XY
Lucas
Joe N
JN
Cheung
Annie L M
AL
D002460:Cell Line; D002869:Chromosome Aberrations; D020223:Chromosome Painting / Q000379:methods* / Q000706:statistics & numerical data; D002877:Chromosomes, Human / Q000235:genetics / Q000502:physiology; D004847:Epithelial Cells / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods* / Q000706:statistics & numerical data; D010053:Ovary / Q000473:pathology*; D016615:Telomere / Q000235:genetics / Q000378:metabolism / Q000502:physiology*