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[Cancer Research 57, 300-303, January 15, 1997]
© 1997 American Association for Cancer Research
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BAT-26, an Indicator of the Replication Error Phenotype in Colorectal Cancers and Cell Lines1

Jean-Marc Hoang, Paul H. Cottu, Benedicte Thuille, Rémi J. Salmon, Gilles Thomas and Richard Hamelin2

Inserm U 434, Génétique des Tumeurs, Institut Curie, 26 rue d'Ulm, 75005 Paris, France

Instability of microsatellites is a hallmark of the DNA replication error phenotype (RER+) due to the inactivation of mismatch repair genes. In humans, microsatellite instability has first been described in colorectal tumors developing in either hereditary nonpolyposis colorectal cancer or sporadic patients. Colorectal tumorigenesis in RER+ and RER- tumors is probably due to distinct mechanisms, and RER+ tumors have a better prognosis than RER- tumors. The study of the RER status of a tumor may thus be important in the future to determine biological prognosis factors and investigate therapeutical strategies. The RER status of 134 primary tumors and 26 cell lines derived from colorectal cancers was established by PCR amplification and analysis of a minimum of 32 microsatellite loci. This characterization allowed us to unambiguously classify 35 primary tumors and 7 cell lines as RER+. Typing of a single poly(A) tract, BAT-26, was sufficient to confirm the RER status of 159 of these 160 tumors and cell lines. Moreover, in DNA from unaffected individuals, normal tissues of a subset of the RER+ patients, and all RER- tumors or cell lines, BAT-26 was quasi-monomorphic, showing only minor size variations. BAT-26 alleles showing shortening from 4 to 15 bp were observed in all but 1 of the RER+ tumors and cell lines. The size difference between the range of normal large alleles and unstable small alleles was sufficient to be detected by electrophoresis on conventional polyacrylamide gels stained with ethidium bromide. We thus propose a simple, low-cost, and rapid method to screen for the RER status of colorectal cancer primary tumors and cell lines, even in the absence of matching normal DNA and, in most cases, without the need for radioactivity. This method could easily be set up in routine laboratories.

1 This work was supported by grants from the Association pour la Recherche contre le Cancer and the Association Française contre les Myopathies. J-M. Hoang was supported by a grant from the Ligue Nationale contre le Cancer.

2 To whom requests for reprints should be addressed. Phone: 33-1-42-34-66-83; Fax: 33-1-42-34-66-30; E-mail: rhamelin@curie.fr.

Received 7/16/96. Accepted 11/14/96.




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J. Alexander, T. Watanabe, T.-T. Wu, A. Rashid, S. Li, and S. R. Hamilton
Histopathological Identification of Colon Cancer with Microsatellite Instability
Am. J. Pathol., February 1, 2001; 158(2): 527 - 535.
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M. L. Slattery, K. Curtin, K. Anderson, K.-N. Ma, L. Ballard, S. Edwards, D. Schaffer, J. Potter, M. Leppert, and W. S. Samowitz
Associations Between Cigarette Smoking, Lifestyle Factors, and Microsatellite Instability in Colon Tumors
J Natl Cancer Inst, November 15, 2000; 92(22): 1831 - 1836.
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K Shitoh, F Konishi, M Miyaki, T Iijima, T Furukawa, T Tsukamoto, and H Nagai
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J. Clin. Pathol., November 1, 2000; 53(11): 841 - 845.
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C. VAURS-BARRIÈRE, F. PENAULT-LLORCA, V. LAPLACE-MARIEZE, N. PRESNEAU, C. M MAUGARD, M. FICHE, A. HARDOUIN, and Y.-J. BIGNON
Low frequency of microsatellite instability in BRCA1 mutated breast tumours
J. Med. Genet., October 1, 2000; 37(10): 32e - 32.
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J M D WHEELER, W F BODMER, and N J M. MORTENSEN
DNA mismatch repair genes and colorectal cancer
Gut, July 1, 2000; 47(1): 148 - 153.
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A. Duval, S. Rolland, E. Tubacher, H. Bui, G. Thomas, and R. Hamelin
The Human T-Cell Transcription Factor-4 Gene: Structure, Extensive Characterization of Alternative Splicings, and Mutational Analysis in Colorectal Cancer Cell Lines
Cancer Res., July 1, 2000; 60(14): 3872 - 3879.
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M. RAVNIK-GLAVAC, U. POTOCNIK, and D. GLAVAC
Incidence of germline hMLH1 and hMSH2 mutations (HNPCC patients) among newly diagnosed colorectal cancers in a Slovenian population
J. Med. Genet., July 1, 2000; 37(7): 533 - 536.
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R. Salovaara, A. Loukola, P. Kristo, H. Kaariainen, H. Ahtola, M. Eskelinen, N. Harkonen, R. Julkunen, E. Kangas, S. Ojala, et al.
Population-Based Molecular Detection of Hereditary Nonpolyposis Colorectal Cancer
J. Clin. Oncol., June 11, 2000; 18(11): 2193 - 2200.
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A. Chao, F. Gilliland, C. Willman, N. Joste, I-M. Chen, N. Stone, J. Ruschulte, D. Viswanatha, P. Duncan, R. Ming, et al.
Patient and Tumor Characteristics of Colon Cancers with Microsatellite Instability: A Population-based Study
Cancer Epidemiol. Biomarkers Prev., June 1, 2000; 9(6): 539 - 544.
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K Yamashita, Y Arimura, S Kurokawa, F Itoh, T Endo, K Hirata, A Imamura, M Kondo, T Sato, and K Imai
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Gut, June 1, 2000; 46(6): 790 - 794.
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I. Gonzalez-Garcia, V. Moreno, M. Navarro, J. Marti-Rague, E. Marcuello, C. Benasco, O. Campos, G. Capella, and M. A. Peinado
Standardized Approach for Microsatellite Instability Detection in Colorectal Carcinomas
J Natl Cancer Inst, April 5, 2000; 92(7): 544 - 549.
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R. Sturzeneker, R. A.U. Bevilacqua, L. A. Haddad, A. J.G. Simpson, and S. D.J. Pena
Microsatellite instability in tumors as a model to study the process of microsatellite mutations
Hum. Mol. Genet., February 12, 2000; 9(3): 347 - 352.
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W. K. Leung, J. J. Kim, J. G. Kim, D. Y. Graham, and A. R. Sepulveda
Microsatellite Instability in Gastric Intestinal Metaplasia in Patients with and without Gastric Cancer
Am. J. Pathol., February 1, 2000; 156(2): 537 - 543.
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M. Esteller, L. Catasus, X. Matias-Guiu, G. L. Mutter, J. Prat, S. B. Baylin, and J. G. Herman
hMLH1 Promoter Hypermethylation Is an Early Event in Human Endometrial Tumorigenesis
Am. J. Pathol., November 1, 1999; 155(5): 1767 - 1772.
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S. A. Kuismanen, M. T. Holmberg, R. Salovaara, P. Schweizer, L. A. Aaltonen, A. de la Chapelle, M. Nystrom-Lahti, and P. Peltomaki
Epigenetic phenotypes distinguish microsatellite-stable and -unstable colorectal cancers
PNAS, October 26, 1999; 96(22): 12661 - 12666.
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A. Duval, J. Gayet, X.-P. Zhou, B. Iacopetta, G. Thomas, and R. Hamelin
Frequent Frameshift Mutations of the TCF-4 Gene in Colorectal Cancers with Microsatellite Instability
Cancer Res., September 1, 1999; 59(17): 4213 - 4215.
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R. Pyatt, R. B. Chadwick, C. K. Johnson, C. Adebamowo, A. de la Chapelle, and T. W. Prior
Polymorphic Variation at the BAT-25 and BAT-26 Loci in Individuals of African Origin : Implications for Microsatellite Instability Testing
Am. J. Pathol., August 1, 1999; 155(2): 349 - 353.
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I M FRAYLING
Microsatellite instability
Gut, July 1, 1999; 45(1): 1 - 4.
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C Lamberti, R Kruse, C Ruelfs, R Caspari, Y Wang, M Jungck, M Mathiak, H R H Malayeri, W Friedl, T Sauerbruch, et al.
Microsatellite instability---a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer
Gut, June 1, 1999; 44(6): 839 - 843.
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S. Schwartz Jr., H. Yamamoto, M. Navarro, M. Maestro, J. Reventos, and M. Perucho
Frameshift Mutations at Mononucleotide Repeats in caspase-5 and Other Target Genes in Endometrial and Gastrointestinal Cancer of the Microsatellite Mutator Phenotype
Cancer Res., June 1, 1999; 59(12): 2995 - 3002.
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W. S. Samowitz, M. L. Slattery, J. D. Potter, and M. F. Leppert
BAT-26 and BAT-40 Instability in Colorectal Adenomas and Carcinomas and Germline Polymorphisms
Am. J. Pathol., June 1, 1999; 154(6): 1637 - 1641.
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G. Deng, A. Chen, J. Hong, H. S. Chae, and Y. S. Kim
Methylation of CpG in a Small Region of the hMLH1 Promoter Invariably Correlates with the Absence of Gene Expression
Cancer Res., May 1, 1999; 59(9): 2029 - 2023.
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 CarcinogenesisHome page
K. Gotoh, Y. Yatabe, T. Sugiura, K. Takagi, M. Ogawa, T. Takahashi, and T. Mitsudomi
Frameshift mutations in TGFßRII, IGFIIR, BAX, hMSH3 and hMSH6 are absent in lung cancers
Carcinogenesis, March 1, 1999; 20(3): 499 - 502.
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M. Perucho, C. R. Boland, S. N. Thibodeau, S. R. Hamilton, D. Sidransky, J. R. Eshleman, R. W. Burt, S. J. Meltzer, M. A. Rodriguez-Bigas, R. Fodde, et al.
Correspondence re: C. R. Boland et al. A National Cancer Institute Workshop on Microsatellite Instability for Cancer Detection and Familial Predisposition: Development of International Criteria for the Determination of Microsatellite Instability in Colorectal Cancer. Cancer Res., 58: 5248-5257, 1998
Cancer Res., January 1, 1999; 59(1): 249 - 256.
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T. Fujiwara, J. M. Stolker, T. Watanabe, A. Rashid, P. Longo, J. R. Eshleman, S. Booker, H. T. Lynch, J. R. Jass, J. S. Green, et al.
Accumulated Clonal Genetic Alterations in Familial and Sporadic Colorectal Carcinomas with Widespread Instability in Microsatellite Sequences
Am. J. Pathol., October 1, 1998; 153(4): 1063 - 1078.
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C. Oliveira, R. Seruca, M. Seixas, and M. Sobrinho-Simoes
The Clinicopathological Features of Gastric Carcinomas with Microsatellite Instability May Be Mediated by Mutations of Different ""Target Genes"" : A Study of the TGFß RII, IGFII R, and BAX Genes
Am. J. Pathol., October 1, 1998; 153(4): 1211 - 1219.
[Abstract] [Full Text] [PDF]

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L. A. Aaltonen, R. Salovaara, P. Kristo, F. Canzian, A. Hemminki, P. Peltomaki, R. B. Chadwick, H. Kaariainen, M. Eskelinen, H. Jarvinen, et al.
Incidence of Hereditary Nonpolyposis Colorectal Cancer and the Feasibility of Molecular Screening for the Disease
N. Engl. J. Med., May 21, 1998; 338(21): 1481 - 1487.
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S. Olschwang, R. Hamelin, P. Laurent-Puig, B. Thuille, Y. De Rycke, Y.-J. Li, F. Muzeau, J. Girodet, R.-J. Salmon, and G. Thomas
Alternative genetic pathways in colorectal carcinogenesis
PNAS, October 28, 1997; 94(22): 12122 - 12127.
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