Summary
Familial adenomatous polyposis (FAP), which includes familial polyposis coli (FPC) and the Gardner syndrome (GS), is a genetically determined premalignant disease of the colon inherited by a locus (APC) mapping within 5q15–q22. To elucidate the role of 5q loss in FAP tumorigenesis, we analysed 51 colorectal tumors and seven desmoids from 19 cases of FPC and five GS patients, as well as 15 sporadic colon cancers. RFLP analysis revealed a high incidence of allelic deletion in hereditary colon cancers as well as in sporadic colon cancers with a peak at the APC locus. APC loss resulted primarily from interstitial deletion or mitotic recombination. Combined tumor and pedigree analysis in a GS family revealed loss of normal 5q alleles in three tumors, including a desmoid tumor, which suggests the involvement of hemizygosity or homozygosity of the defective APC gene in colon carcinogenesis and, possibly, in extracolonic neoplasms associated with FAP.
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Ashton-Rickardt PG, Dunlop MG, Nakamura Y, Morris RG, Purdie CA, Steel CM, Evans HJ, Bird CC, Wyllie AH (1989) High frequency of APC loss in sporadic colorectal carcinoma due to breaks clustered in 5q21–22. Oncogene 4:1169–1174
Bailey CJ, Rider SH, Bodmer WF (1987) A new RFLP for L1.4 (D5S4) an anonymous genomic clone localised to chromosome 5. Nucleic Acids Res 15:6762
Barker D, Schafer M, White R (1984) Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell 36:131–138
Bodmer WF, Bailey CJ, Bodmer J, Bussey HJR, Ellis A, Gorman P, Lucibello FC, Murday VA, Rider SH, Scambler P, Sheer D, Solomon E, Spurr NK (1987) Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature 328:614–616
Cavenee WK, Hansen MF, Nordenskjöld M, Kock E, Maumenee I, Squire JA, Phillips RA, Gallie B (1985) Genetic origin of mutations predisposing to retinoblastoma. Science 228:501–503
De Qi Xu, Guilhot S, Galibert F (1985) Restriction fragment length polymorphism of the human c-fms gene. Proc Natl Acad Sci USA 82:2862–2865
Dietzsch E, Retief AE, Lotze MJ, Warnich L, Nicholson DL, Fox MF, Fricke J, Plessis L du, Oosthuizen CJJ (1986) An anonymous human single copy genomic clone, D5S6 (M4) on chromosome 5 identifies a three allele RFLP. Nucleic Acids Res 14:1923
Feinberg AP, Vogelstein B (1983) A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13
Friedman E, Sakaguchi K, Bale AE, Falchetti A, Streeten E, Zimering M, Weinstein LS, McBride WO, Nakamura Y, Brandi M-L, Norton JA, Aurbach GD, Spiegel AM, Marx SJ (1989) Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. N Engl J Med 321:213–218
Hansen MF, Cavenee WK (1988) Retinoblastoma and the progression of tumor genetics. Trends Genet 4:125–128
Jagelman DG (1987) Extracolonic manifestations of familial polyposis coli. Cancer Genet Cytogenet 27:319–325
Landsvater RM, Mathew CGP, Smith BA, Marcus EM, Meerman GJTe, Lips CJM, Geerdink RA, Nakamura Y, Ponder BAJ, Buys CHC (1989) Development of multiple endocrine neoplasia type 2A does not involve substantial deletions of chromosome 10. Genomics 4:246–250
Larsson C, Skogseid B, Öberg K, Nakamura Y, Nordenskjöld M (1988) Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332:85–87
Law DJ, Olschwang S, Monpezat J-P, Lefrancois D, Jagelman D, Petrelli NJ, Thomas G, Feinberg AP (1988) Concerted nonsyntenic allelic loss in human colorectal carcinoma. Science 241:961–965
Leppert M, Dobbs P, Scambler P, O'Connell P, Nakamura Y, Stauffer D, Woodward S, Burt R, Hughes J, Gardner E, Lathrop M, Wasmuth J, Lalouel J-M, White R (1987a) The gene for familial polyposis coli maps to the long arm of chromosome 5. Science 238:1411–1413
Leppert M, Wasmuth J, Overhauser J, Dobbs M, Nakamura Y, Lathrop M, O'Connell P, Cartwright P, Lalouel JM, White R (1987b) A primary genetic linkage map of chromosome 5 (abstract). (9th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 46:649
Mathew CGP, Smith BA, Thorpe K, Wong Z, Royle NJ, Jeffreys AJ, Ponder BAJ (1987) Deletion of genes on chromosome 1 in endocrine neoplasia. Nature 328:524–526
Muleris M, Salmon RJ, Zafrani B, Girodet J, Dutrillaux B (1985) Consistent deficiencies of chromosome 18 and of the short arm of chromosome 17 in eleven cases of human large bowel cancer: a possible recessive determinism. Ann Génét (Paris) 28:206–213
Nakamura Y, Lathrop M, Leppert M, Dobbs M, Wasmuth J, Wolff E, Carlson M, Fujimoto E, Krapcho K, Sears T, Woodward S, Hughes J, Burt R, Gardner E, Lalouel J-M, White R (1988) Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet 43:638–644
Nelkin BD, Nakamura Y, White RW, Bustros AC de, Herman J, Wells SA, Baylin SB (1989) Low incidence of loss of chromosome 10 in sporadic and hereditary human medullary thyroid carcinoma. Cancer Res 49:4114–4119
Okamoto M, Sasaki M, Sugio K, Sato C, Iwama T, Ikeuchi T, Tonomura A, Sasazuki T, Miyaki M (1988) Loss of constitutional heterozygosity in colon carcinoma from patients with familial polyposis coli. Nature 331:273–277
Okamoto M, Sato C, Iwama T, Miyaki M (1990) Loss of alleles in patients with familial adenomatous polyposis and colon cancers. In: Herrela L (ed) Familial adenomatous polyposis. Liss, New York, pp 383–391
Pearson PL, Kidd KK, Willard HF (1987) Report of the committee on human gene mapping by recombinant DNA techniques. (9th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 46:390–566
Reichmann A, Martin P, Levin B (1981) Chromosomal banding patterns in human large bowel cancer. Int J Cancer 28:431–440
Reichmann A, Martin P, Levin B (1985) Marker chromosomes in direct preparations of human large bowel tumors. Cancer Genet Cytogenet 16:229–233
Royle NJ, Clarkson RE, Wong Z, Jeffreys AJ (1988) Clustering of hypervariable minisatellites in the proterminal regions of uman autosomes. Genomics 3:352–360
Skolnick MH, Willard HF, Menlove LA (1984) Report of the committee on human gene mapping by recombinant DNA techniques. (7th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 37:210–273
Solomon E, Voss R, Hall V, Bodmer WF, Jass JR, Jeffreys AJ, Lucibello EC, Patel I, Rider SH (1987) Chromosome 5 allele loss in human colorectal carcinomas. Nature 328:616–619
Stewart GD, Bruns GAP, Wasmuth JJ, Kurnit DM (1987) An anonymous DNA segment (Pi227) maps to the long arm of human chromosome 5 and identifies a BstXI polymorphism (D5S26). Nucleic Acids Res 15:3939
Thakker RV, Bouloux P, Wooding C, Chotai K, Broad PM, Spurr NK, Besser GM, O'Riordan LH (1989) Association of parathyroid tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11. N Engl J Med 321:218–224
Utsunomiya J (1988) Pathological and genetic aspects of adenomatosis coli in Japan. In: Takebe H, Utsunomiya J (eds) Genetics of human tumors in Japan. (Gann Monograph on Cancer Research, vol 35) Japan Scientific Societies Press, Tokyo, pp 45–62
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM, Bos JL (1988) Genetic alterations during colorectal tumor development. N Engl J Med 319:525–532
Wong Z, Wilson V, Patel I, Povey S, Jeffreys AJ (1987) Characterization of a panel of highly variable minisatellites cloned from human DNA. Ann Hum Genet 51:269–288
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Okamoto, M., Sato, C., Kohno, Y. et al. Molecular nature of chromosome 5q loss in colorectal tumors and desmoids from patients with familial adenomatous polyposis. Hum Genet 85, 595–599 (1990). https://doi.org/10.1007/BF00193581
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DOI: https://doi.org/10.1007/BF00193581