Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array-CGH

被引:55
作者
Ichimura, K
Mungall, AJ
Fiegler, H
Pearson, DM
Dunham, I
Carter, NP
Collins, VP
机构
[1] Univ Cambridge, Addenbrookes Hosp, Dept Pathol, Div Mol Histopathol, Cambridge CB2 2QQ, England
[2] Wellcome Trust Sanger Inst, Cambridge, England
基金
英国惠康基金;
关键词
brain tumour; molecular cytogenetics; array-CGH; glioblastoma; astrocytoma;
D O I
10.1038/sj.onc.1209156
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Deletions of chromosome 6 are a common abnormality in diverse human malignancies including astrocytic tumours, suggesting the presence of tumour suppressor genes (TSG). In order to help identify candidate TSGs, we have constructed a chromosome 6 tile path microarray. The array contains 1780 clones (778 P1-derived artificial chromosome and 1002 bacterial artificial chromosome) that cover 98.3% of the published chromosome 6 sequences. A total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30 anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using this array. Single copy number change was successfully detected and the result was in general concordant with a microsatellite analysis. The pattern of copy number change was complex with multiple interstitial deletions/ gains. However, a predominance of telomeric 6q deletions was seen. Two small common and overlapping regions of deletion at 6q26 were identified. One was 1002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, AR1D1B. The data show that the chromosome 6 tile path array is useful in mapping copy number changes with high resolution and accuracy. We confirmed the high frequency of chromosome 6 deletions in AA and GB, and identified two novel commonly deleted regions that may harbour TSGs.
引用
收藏
页码:1261 / 1271
页数:11
相关论文
共 43 条
[21]   A tiling resolution DNA microarray with complete coverage of the human genome [J].
Ishkanian, AS ;
Malloff, CA ;
Watson, SK ;
deLeeuw, RJ ;
Chi, B ;
Coe, BP ;
Snijders, A ;
Albertson, DG ;
Pinkel, D ;
Marra, MA ;
Ling, V ;
MacAulay, C ;
Lam, WL .
NATURE GENETICS, 2004, 36 (03) :299-303
[22]   MULTIPLE POLYMORPHISMS, BUT NO MUTATIONS, IN THE WAF1/CIP1 GENE IN HUMAN BRAIN-TUMORS [J].
KOOPMANN, J ;
MAINTZ, D ;
SCHILD, S ;
SCHRAMM, J ;
LOUIS, DN ;
WIESTLER, OD ;
VONDEIMLING, A .
BRITISH JOURNAL OF CANCER, 1995, 72 (05) :1230-1233
[23]   Expression of Hqk encoding a KH RNA binding protein is altered in human glioma [J].
Li, ZZ ;
Kondo, T ;
Murata, T ;
Ebersole, TA ;
Nishi, T ;
Tada, K ;
Ushio, Y ;
Yamamura, K ;
Abe, K .
JAPANESE JOURNAL OF CANCER RESEARCH, 2002, 93 (02) :167-177
[24]   The complexity of the 7p12 amplicon in human astrocytic gliomas: Detailed mapping of 246 tumors [J].
Liu, L ;
Ichimura, K ;
Pettersson, EH ;
Goike, HM ;
Collins, VP .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2000, 59 (12) :1087-1093
[25]   The human homologue of unc-93 maps to chromosome 6q27 -: characterisation and analysis in sporadic epithelial ovarian cancer -: art. no. 20 [J].
Liu, Y ;
Dodds, P ;
Emilion, G ;
Mungall, AJ ;
Dunham, I ;
Beck, S ;
Wells, RS ;
Charnock, FML ;
Ganesan, TS .
BMC GENETICS, 2002, 3 (1)
[26]  
Miyakawa A, 2000, BRIT J CANCER, V82, P543
[27]   The DNA sequence and analysis of human chromosome 6 [J].
Mungall, AJ ;
Palmer, SA ;
Sims, SK ;
Edwards, CA ;
Ashurst, JL ;
Wilming, L ;
Jones, MC ;
Horton, R ;
Hunt, SE ;
Scott, CE ;
Gilbert, JGR ;
Clamp, ME ;
Bethel, G ;
Milne, S ;
Ainscough, R ;
Almeida, JP ;
Ambrose, KD ;
Andrews, TD ;
Ashwell, RIS ;
Babbage, AK ;
Bagguley, CL ;
Bailey, J ;
Banerjee, R ;
Barker, DJ ;
Barlow, KF ;
Bates, K ;
Beare, DM ;
Beasley, H ;
Beasley, O ;
Bird, CP ;
Blakey, S ;
Bray-Allen, S ;
Brook, J ;
Brown, AJ ;
Brown, JY ;
Burford, DC ;
Burrill, W ;
Burton, J ;
Carder, C ;
Carter, NP ;
Chapman, JC ;
Clark, SY ;
Clark, G ;
Clee, CM ;
Clegg, S ;
Cobley, V ;
Collier, RE ;
Collins, JE ;
Colman, LK ;
Corby, NR .
NATURE, 2003, 425 (6960) :805-U1
[28]   Fragile and unstable chromosomes in cancer: causes and consequences [J].
Richards, RI .
TRENDS IN GENETICS, 2001, 17 (06) :339-345
[29]   The SWI/SNF complex - Chromatin and cancer [J].
Roberts, CWM ;
Orkin, SH .
NATURE REVIEWS CANCER, 2004, 4 (02) :133-142
[30]   Large-scale copy number polymorphism in the human genome [J].
Sebat, J ;
Lakshmi, B ;
Troge, J ;
Alexander, J ;
Young, J ;
Lundin, P ;
Måner, S ;
Massa, H ;
Walker, M ;
Chi, MY ;
Navin, N ;
Lucito, R ;
Healy, J ;
Hicks, J ;
Ye, K ;
Reiner, A ;
Gilliam, TC ;
Trask, B ;
Patterson, N ;
Zetterberg, A ;
Wigler, M .
SCIENCE, 2004, 305 (5683) :525-528