Abstract
Molecular, functional, and clinical analyses strongly suggest that chromosome segment 11p15.5 contains a gene involved in lung cancer pathogenesis. The critical region of allele loss is 310 kb in size. We used our contig of P1-phage artificial chromosome (PAC) clones together with newly identified bacterial artificial chromosome (BAC) clones and the draft human genome sequence to complete a contiguous string of 380 407 bp. Three PAC clones that span the region were used to identify transcripts by exon trapping. Computational gene prediction algorithms were used to query the sequence for potential genes and exons. Screening for expression was performed with tissue-specific and cell line derived mRNA arrays. The region contains the complete SSA/Ro52 and RRM1 genes, exons 7–12 of the GOK gene, and the ψrad pseudo-gene. A cluster of six nearly identical genes with an intact open reading frame (ORF) of 585 bp that share 75% identity with the HSPC182 gene was found. In addition, five putative novel genes were identified. Sequence tagged sites (STS) and polymorphic markers were used to screen 117 lung cancer cell lines for homozygous deletions and none were identified. These data provide the basis for the identification of a lung cancer suppressor gene on 11p15.5.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ali IU, Lidereau R, Theillet C, Callahan R . 1987 Science 238: 185–188
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ . 1990 J. Mol. Biol. 215: 403–410
Bepler G, Fong KM, Johnson BE, O'Briant KC, Daly LA, Zimmerman PV, Garcia-Blanco MA, Peterson B . 1998 Cancer Detect. Prev. 22: 1–6
Bepler G, Garcia-Blanco MA . 1994 Proc. Natl. Acad. Sci. USA 91: 5513–5517
Bepler G, Jaques G, Neumann K, Aumueller G, Gropp C, Havemann K . 1987 J. Cancer Res. Clin. Oncol. 113: 31–40
Bepler G, Koehler A . 1995 Cancer Genet. Cytogenet. 84: 25–30
Bepler G, Koehler A, Kiefer P, Havemann K, Beisenherz K, Jaques G, Gropp C, Haeder M . 1988 Differentiation 37: 158–171
Bepler G, McIntyre LM, Kim YC, Pitterle DM. . 2000 Proc. Am. Soc. Clin Oncol. 19,: 485a
Bepler G, O'Briant K, Kim Y, Schreiber G, Pitterle D . 1999 Genomics 55: 164–175
Bork P, Copley R . 2001 Nature 409: 818–820
Burge C, Karlin S . 1997 J. Mol. Biol. 268: 78–94
Burn TC, Connors TD, Klinger KW, Landes GM . 1995 Gene 161: 183–187
Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW, Zweig MH, Minna JD . 1985 Cancer Research 45: 2913–2923
Chenchik A, Diachenko L, Moqadam F, Tarabykin V, Lukyanov S, Siebert PD . 1996 Biotech. 21: 526–534
Church DM, Stotler CJ, Rutter JL, Murrell JR, Trofatter JA, Buckler AJ . 1994 Nature Gene. 6: 98–105
Consortium, International Human Genome Sequencing Consortium . 2001 Nature 409: 860–921
Dickson D . 1999 Nature 401: 311
Elledge SJ, Zhou Z, Allen JB . 1992 Trends Biochem. Sci. 17: 119–123
Fearon ER, Feinberg AP, Hamilton SH, Vogelstein B . 1985 Nature 318: 377–380
Fong KM, Zimmerman PV, Smith PJ . 1994 Genes Chrom. Cancer 10: 183–189
Frengen E, Weichenham D, Zhao B, Osoegawa K, Geel M, deJong P . 1999 Genomics 58: 250–253
Greenlee RT, Hill-Harmon MB, Murray T, Thun M . 2001 CA Cancer J. Clin. 51: 15–36
Ioannou P, Amemiya C, Garnes J, Kroisel P, Shizuya H, Chen C, Batzer M, Dejong P . 1994 Nature Genet. 6: 84–89
Karnik P, Paris M, Williams BRG, Casey G, Crowe J, Chen P . 1998 Hum. Mol. Genet. 7: 895–903
Kim YC, Cao Y, Pitterle DM, O'Briant KC, Bepler G . 2000 Int. J. Cancer 87: 61–67
Lu K, Weitzel J, Kodali S, Welch W, Berkowitz R, Mok S . 1997 Cancer Res. 57: 387–390
Ludwig CU, Raefle G, Dalquen P, Stulz P, Stahel R, Obrecht JP . 1991 Int. J. Cancer 49: 661–665
Lukeis R, Irving L, Garson M, Hasthorpe S . 1990 Genes Chrom. Cancer 2: 116–124
Matz M, Shagin D, Bogdanova E, Britanova O, Lukyanov S, Diatchenko L, Chenchik A . 1999 Nucleic Acids Res. 27: 1558–1560
O'Briant K, Jolicoeur E, Garst J, Campa M, Schreiber G, Bepler G . 1997 Anticancer Res. 17: 3243–3252
Phelps RM, Johnson BE, Ihde DC, Gazdar AF, Carbone DP, McClintock PR, Linnoila RI, Matthews MJ, Bunn Jr PA, Carney D, Minna JD, Mulshine JL . 1996 J. Cell Biochem. Suppl. 24: 32–91
Pitterle DM, Kim YC, Cao Y, Gautam A, Zhao B, Beck AF, Bepler G . 2000 Current Genomics 1: 281–288
Pitterle DM, Kim YC, Jolicoeur EMC, Cao Y, O'Briant KC, Bepler G . 1999 Mamm. Genome 10: 916–922
Ranzani GN, Renault B, Pellegatta NS, Fattorini P, Magni E, Bacci F, Amadori D . 1993 Hum. Genet 92: 244–249
Reese MG, Kulp D, Tammana H, Haussler D . 2000 Genome Res. 10: 529–538
Satoh H, Lamb PW, Dong J-T, Everitt J, Boreiko C, Oshimura M, Barrett JC . 1993 Molec. Carcinogen. 7: 157–164
Shibagaki I, Shimada Y, Wagata T, Ikenaga M, Imamura M, Ishizaki K . 1994 Cancer Res. 54: 2996–3000
Shiraishi M, Morinaga S, Noguchi M, Shimosato Y, Sekiya T . 1987 Jpn. J. Cancer Res. 78: 1302–1308
Skinner MA, Vollmer R, Huper G, Abbott P, Iglehart JD . 1990 Cancer Res. 50: 2303–2306
Stubbe J . 1998 Proc. Natl. Acad. Sci. USA 95: 2723–2724
Tran YK, Newsham IF . 1996 Cancer Res. 56: 2916–2921
Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K, Haase VH, Ambrose CM, Munroe D, Bove C, Haines JL, Martuza L, MacDonald ME, Seizinger BR, Short MP, Buckler AJ, Gusella JF . 1993 Cell 72: 791–800
Uberbacher EC, Xu Y, Mural RJ . 1996 Methods Enzymol. 266: 259–281
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C et al. 2001 Science 291: 1304–1351
Viel A, Giannini F, Tumiotto L, Sopracaordevole F, Vistein MC, Biocchi M . 1992 Br. J. Cancer 66: 1030–1036
Weston A, Willey JC, Modali R, Sugimura H, McDowell EM, Resau J, Light B, Haugen A, Mann DL, Trump BF, Harris CC . 1989 Proc. Natl. Acad. Sci. USA 86: 5099–5103
Whang-Peng J, Knutsen T, Gazdar A, Steinberg SM, Oie H, Linnoila I, Mulshine J, Nau M, Minna JD . 1991 Genes Chromosom. Cancer 3: 168–188
Winqvist R, Mannermaa A, Alavaikko M, Blanco G, Taskinen PJ, Kiviniemi K, Newsham I, Cavenee W . 1993 Cancer Res. 53: 4486–4488
Zhumabayeva B, Chenchik A, Sieert PD . 1999 Biotech. 27: 834–836
Acknowledgements
We thank David Chervinsky for allelotyping of the lung cancer cell lines and Drs Arvind Virmani and Adi Gazdar for providing DNA from lung cancer cell lines. We thank Drs John Cowell and Thomas Shows for helpful suggestions during the preparation of the manuscript. This work was supported by grants from the National Cancer Institute (5RO1 CA 70317) and the Roswell Park Cancer Center Support Grant (P30 CA 16056).
Accession Numbers
The DNA sequence was deposited in the EMBL database under Accession numbers AF391283, AF391284 and AF391285.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhao, B., Bepler, G. Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer. Oncogene 20, 8154–8164 (2001). https://doi.org/10.1038/sj.onc.1205027
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205027
Keywords
This article is cited by
-
Polymorphisms in CARS are associated with gastric cancer risk: a two-stage case–control study in the Chinese population
Gastric Cancer (2017)
-
RRM1-induced metastasis suppression through PTEN-regulated pathways
Oncogene (2003)
-
Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer
Oncogene (2003)