Human Molecular Genetics, Vol 6, 193-203, Copyright © 1997 by Oxford University Press
F Boldog, RM Gemmill, J West, M Robinson, L Robinson, E Li, J Roche, S Todd, B Waggoner, R Lundstrom, J Jacobson, MR Mullokandov, H Klinger and HA Drabkin
Loss of heterozygosity (LOH) involving 3p occurs in many carcinomas but is
complicated by the identification of four distinct homozygous deletion
regions. One putative target, 3p14.2, contains the common fragile site,
FRA3B, a hereditary renal carcinoma-associated 3;8 translocation and the
candidate tumor suppressor gene, FHIT. Using a approximately 300 kb
comsid/lambda contig, we identified homozygous deletions in cervix, breast,
lung and colorectal carcinoma cell lines. The smallest deletion (CC19) was
shown not to involve FHIT coding exons and no DNA sequence alterations were
present in the transcript. We also detected discontinuous deletions as well
as deletions in non-tumor DNAs, suggesting that FHIT is not a selective
target. Further, we demonstrate that some reported FHIT aberrations
represent normal splicing variation. DNA sequence analysis of 110 kb
demonstrated that the region is high in A-T content, LINEs and MER repeats,
whereas Alu elements are reduced. We note an intriguing similarity in
repeat sequence composition between FRA3B and a 152 kb segment from the
Fragile-X region. We also identified similarity between a FRA3B segment and
a small polydispersed circular DNA. In contrast to the selective loss of a
tumor suppressor gene, we propose an alternative hypothesis, that some
putative targets including FRA3B may undergo loss as a consequence of
genomic instability. This instability is not due to DNA mismatch repair
deficiency, but may correlate in part with p53 inactivation.
ARTICLES
Chromosome 3p14 homozygous deletions and sequence analysis of FRA3B
Division of Medical Oncology, University of Colorado Health Sciences Center, Denver 80262, USA.
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
S. G. Durkin, R. L. Ragland, M. F. Arlt, J. G. Mulle, S. T. Warren, and T. W. Glover Replication stress induces tumor-like microdeletions in FHIT/FRA3B PNAS, January 8, 2008; 105(1): 246 - 251. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. W. Glover, M. F. Arlt, A. M. Casper, and S. G. Durkin Mechanisms of common fragile site instability Hum. Mol. Genet., October 15, 2005; 14(suppl_2): R197 - R205. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Mulvihill and Y.-H. Wang Two Breakpoint Clusters at Fragile Site FRA3B Form Phased Nucleosomes Genome Res., July 1, 2004; 14(7): 1350 - 1357. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Kim, Y. M. Kwon, J. S. Kim, H. Lee, J.-H. Park, Y. M. Shim, J. Han, J. Park, and D.-H. Kim Tumor-Specific Methylation in Bronchial Lavage for the Early Detection of Non-Small-Cell Lung Cancer J. Clin. Oncol., June 15, 2004; 22(12): 2363 - 2370. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ciullo, M.-A. Debily, L. Rozier, M. Autiero, A. Billault, V. Mayau, S. El Marhomy, J. Guardiola, A. Bernheim, P. Coullin, et al. Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I Hum. Mol. Genet., November 1, 2002; 11(23): 2887 - 2894. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Corbin, M. E. Neilly, R. Espinosa III, E. M. Davis, T. W. McKeithan, and M. M. Le Beau Identification of Unstable Sequences within the Common Fragile Site at 3p14.2: Implications for the Mechanism of Deletions within Fragile Histidine Triad Gene/Common Fragile Site at 3p14.2 in Tumors Cancer Res., June 1, 2002; 62(12): 3477 - 3484. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. I. Wistuba, R. Ashfaq, A. Maitra, H. Alvarez, E. Riquelme, and A. F. Gazdar Fragile Histidine Triad Gene Abnormalities in the Pathogenesis of Gallbladder Carcinoma Am. J. Pathol., June 1, 2002; 160(6): 2073 - 2079. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Maitra, I. I. Wistuba, C. Washington, A. K. Virmani, R. Ashfaq, S. Milchgrub, A. F. Gazdar, and J. D. Minna High-Resolution Chromosome 3p Allelotyping of Breast Carcinomas and Precursor Lesions Demonstrates Frequent Loss of Heterozygosity and a Discontinuous Pattern of Allele Loss Am. J. Pathol., July 1, 2001; 159(1): 119 - 130. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. D. Kholodnyuk, A. Szeles, Y. Yang, G. Klein, and S. Imreh Inactivation of the Human Fragile Histidine Triad Gene at 3p14.2 in Monochromosomal Human/Mouse Microcell Hybrid-derived Severe Combined Immunodeficient Mouse Tumors Cancer Res., December 1, 2000; 60(24): 7119 - 7125. [Abstract] [Full Text] |
||||
![]() |
K. Ried, M. Finnis, L. Hobson, M. Mangelsdorf, S. Dayan, J. K. Nancarrow, E. Woollatt, G. Kremmidiotis, A. Gardner, D. Venter, et al. Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells Hum. Mol. Genet., July 1, 2000; 9(11): 1651 - 1663. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. I. Wistuba, C. Behrens, A. K. Virmani, G. Mele, S. Milchgrub, L. Girard, J. W. Fondon III, H. R. Garner, B. McKay, F. Latif, et al. High Resolution Chromosome 3p Allelotyping of Human Lung Cancer and Preneoplastic/Preinvasive Bronchial Epithelium Reveals Multiple, Discontinuous Sites of 3p Allele Loss and Three Regions of Frequent Breakpoints Cancer Res., April 1, 2000; 60(7): 1949 - 1960. [Abstract] [Full Text] |
||||
![]() |
M. Mangelsdorf, K. Ried, E. Woollatt, S. Dayan, H. Eyre, M. Finnis, L. Hobson, J. Nancarrow, D. Venter, E. Baker, et al. Chromosomal Fragile Site FRA16D and DNA Instability in Cancer Cancer Res., March 1, 2000; 60(6): 1683 - 1689. [Abstract] [Full Text] |
||||
![]() |
A. J. W. Paige, K. J. Taylor, A. Stewart, J. G. Sgouros, H. Gabra, G. C. Sellar, J. F. Smyth, D. J. Porteous, and J. E. V. Watson A 700-kb Physical Map of a Region of 16q23.2 Homozygously Deleted in Multiple Cancers and Spanning the Common Fragile Site FRA16D Cancer Res., March 1, 2000; 60(6): 1690 - 1697. [Abstract] [Full Text] |
||||
![]() |
R. Wu, D. C. Connolly, R. L. Dunn, and K. R. Cho Restored Expression of Fragile Histidine Triad Protein and Tumorigenicity of Cervical Carcinoma Cells J Natl Cancer Inst, February 16, 2000; 92(4): 338 - 344. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Gramantieri, P. Chieco, M. Di Tomaso, L. Masi, F. Piscaglia, S. Brillanti, S. Gaiani, M. Valgimigli, A. Mazziotti, and L. Bolondi Aberrant Fragile Histidine Triad Gene Transcripts in Primary Hepatocellular Carcinoma and Liver Cirrhosis Clin. Cancer Res., November 1, 1999; 5(11): 3468 - 3475. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Julicher, G. Marquitan, N. Werner, W. Bardenheuer, L. Vieten, F. Brocker, H. Topal, S. Seeber, B. Opalka, and J. Schutte Novel Tumor Suppressor Locus in Human Chromosome Region 3p14.2 J Natl Cancer Inst, September 15, 1999; 91(18): 1563 - 1568. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Hallas, M. Albitar, J. Letofsky, M. J. Keating, K. Huebner, and C. M. Croce Loss of FHIT Expression in Acute Lymphoblastic Leukemia Clin. Cancer Res., September 1, 1999; 5(9): 2409 - 2414. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Kohno and J. Yokota1 How many tumor suppressor genes are involved in human lung carcinogenesis? Carcinogenesis, August 1, 1999; 20(8): 1403 - 1410. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Rosell, R. Calvo, J. J. Sanchez, J. Maurel, M. Guillot, M. Monzo, L. Nunez, and A. Barnadas Genetic Susceptibility Associated with Rare HRAS1 Variable Number of Tandem Repeats Alleles in Spanish Non-Small Cell Lung Cancer Patients Clin. Cancer Res., July 1, 1999; 5(7): 1849 - 1854. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Mimori, T. Druck, H. Inoue, H. Alder, L. Berk, M. Mori, K. Huebner, and C. M. Croce Cancer-specific chromosome alterations in the constitutive fragile region FRA3B PNAS, June 22, 1999; 96(13): 7456 - 7461. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Croce, G. Sozzi, and K. Huebner Role of FHIT in Human Cancer J. Clin. Oncol., May 1, 1999; 17(5): 1618 - 1618. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S. Turker, B. M. Gage, J. A. Rose, D. Elroy, O. N. Ponomareva, P. J. Stambrook, and J. A. Tischfield A Novel Signature Mutation for Oxidative Damage Resembles a Mutational Pattern Found Commonly in Human Cancers Cancer Res., April 1, 1999; 59(8): 1837 - 1839. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Gemmill, J. D. West, F. Boldog, N. Tanaka, L. J. Robinson, D. I. Smith, F. Li, and H. A. Drabkin The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8 PNAS, August 4, 1998; 95(16): 9572 - 9577. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Mishmar, A. Rahat, S. W. Scherer, G. Nyakatura, B. Hinzmann, Y. Kohwi, Y. Mandel-Gutfroind, J. R. Lee, B. Drescher, D. E. Sas, et al. Molecular characterization of a common fragile site (FRA7H) on human chromosome 7 by the cloning of a simian virus 40 integration site PNAS, July 7, 1998; 95(14): 8141 - 8146. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. C. Pace, P. N. Garrison, A. K. Robinson, L. D. Barnes, A. Draganescu, A. Rosler, G. M. Blackburn, Z. Siprashvili, C. M. Croce, K. Huebner, et al. Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit PNAS, May 12, 1998; 95(10): 5484 - 5489. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Palin, R Critcher, D. Fitzgerald, J. Anderson, and C. Farr Direct cloning and analysis of DNA sequences from a region of the Chinese hamster genome associated with aphidicolin-sensitive fragility J. Cell Sci., January 6, 1998; 111(12): 1623 - 1634. [Abstract] [PDF] |
||||
![]() |
H. Inoue, H. Ishii, H. Alder, E. Snyder, T. Druck, K. Huebner, and C. M. Croce Sequence of the FRA3B common fragile region: Implications for the mechanism of FHIT deletion PNAS, December 23, 1997; 94(26): 14584 - 14589. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Siprashvili, G. Sozzi, L. D. Barnes, P. McCue, A. K. Robinson, V. Eryomin, L. Sard, E. Tagliabue, A. Greco, L. Fusetti, et al. Replacement of Fhit in cancer cells suppresses tumorigenicity PNAS, December 9, 1997; 94(25): 13771 - 13776. [Abstract] [Full Text] [PDF] |
||||









