Abstract
The tumor suppressor gene APC was recently identified, and the cDNA was cloned from chromosome 5q21. Point mutations affecting APC are seen in the hereditary syndrome familial adenomatous polyposis, and point mutations in APC and a closely linked gene, MCC, as well as loss of heterozygosity involving chromosome 5q have been reported in sporadic colon cancer. To our knowledge, loss of heterozygosity involving APC or MCC or both has not yet been described in any other human cancer besides lung cancer. We used the polymerase chain reaction and DNA content flow cytometric nuclear sorting to examine 30 primary human esophageal cancers for loss of heterozygosity of APC or MCC or both. Loss of one allele was detected in 77% of 26 informative cases. These data suggest that loss of heterozygosity of regions on 5q including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers. They imply that inactivation of APC, MCC, and/or a linked gene on chromosome 5q plays a role in the pathogenesis of some cancers of the upper gastrointestinal tract, as well as in colon cancer and familial adenomatous polyposis.
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- Ashton-Rickardt P. G., Wyllie A. H., Bird C. C., Dunlop M. G., Steel C. M., Morris R. G., Piris J., Romanowski P., Wood R., White R. MCC, a candidate familial polyposis gene in 5q.21, shows frequent allele loss in colorectal and lung cancer. Oncogene. 1991 Oct;6(10):1881–1886. [PubMed] [Google Scholar]
- Atkin N. B., Fox M. F. 5q deletion. The sole chromosome change in a carcinoma of the bladder. Cancer Genet Cytogenet. 1990 May;46(1):129–131. doi: 10.1016/0165-4608(90)90019-7. [DOI] [PubMed] [Google Scholar]
- Blount P. L., Ramel S., Raskind W. H., Haggitt R. C., Sanchez C. A., Dean P. J., Rabinovitch P. S., Reid B. J. 17p allelic deletions and p53 protein overexpression in Barrett's adenocarcinoma. Cancer Res. 1991 Oct 15;51(20):5482–5486. [PubMed] [Google Scholar]
- Bodmer W. F., Bailey C. J., Bodmer J., Bussey H. J., Ellis A., Gorman P., Lucibello F. C., Murday V. A., Rider S. H., Scambler P. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature. 1987 Aug 13;328(6131):614–616. doi: 10.1038/328614a0. [DOI] [PubMed] [Google Scholar]
- Boynton R. F., Huang Y., Blount P. L., Reid B. J., Raskind W. H., Haggitt R. C., Newkirk C., Resau J. H., Yin J., McDaniel T. Frequent loss of heterozygosity at the retinoblastoma locus in human esophageal cancers. Cancer Res. 1991 Oct 15;51(20):5766–5769. [PubMed] [Google Scholar]
- Bullerdiek J., Vollrath M., Wittekind C., Caselitz J., Bartnitzke S. Mucoepidermoid tumor of the parotid gland showing a translocation (3;8)(p21;q12) and a deletion (5)(q22) as sole chromosome abnormalities. Cancer Genet Cytogenet. 1990 Nov 1;50(1):161–164. doi: 10.1016/0165-4608(90)90250-e. [DOI] [PubMed] [Google Scholar]
- Dal Cin P., Li F. P., Prout G. R., Jr, Huben R. P., Limon J., Ferti-Passantonopoulou A., Richie J. P., Sandberg A. A. Involvement of chromosomes 3 and 5 in renal cell carcinoma. Cancer Genet Cytogenet. 1988 Oct 1;35(1):41–46. doi: 10.1016/0165-4608(88)90119-7. [DOI] [PubMed] [Google Scholar]
- Franceschi S., Talamini R., Barra S., Barón A. E., Negri E., Bidoli E., Serraino D., La Vecchia C. Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy. Cancer Res. 1990 Oct 15;50(20):6502–6507. [PubMed] [Google Scholar]
- Fujimori M., Tokino T., Hino O., Kitagawa T., Imamura T., Okamoto E., Mitsunobu M., Ishikawa T., Nakagama H., Harada H. Allelotype study of primary hepatocellular carcinoma. Cancer Res. 1991 Jan 1;51(1):89–93. [PubMed] [Google Scholar]
- Goelz S. E., Hamilton S. R., Vogelstein B. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun. 1985 Jul 16;130(1):118–126. doi: 10.1016/0006-291x(85)90390-0. [DOI] [PubMed] [Google Scholar]
- Groden J., Thliveris A., Samowitz W., Carlson M., Gelbert L., Albertsen H., Joslyn G., Stevens J., Spirio L., Robertson M. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. doi: 10.1016/0092-8674(81)90021-0. [DOI] [PubMed] [Google Scholar]
- Hamilton S. R., Smith R. R., Cameron J. L. Prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction. Hum Pathol. 1988 Aug;19(8):942–948. doi: 10.1016/s0046-8177(88)80010-8. [DOI] [PubMed] [Google Scholar]
- Hamilton S. R., Smith R. R., Cameron J. L. Prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction. Hum Pathol. 1988 Aug;19(8):942–948. doi: 10.1016/s0046-8177(88)80010-8. [DOI] [PubMed] [Google Scholar]
- Herrera L., Kakati S., Gibas L., Pietrzak E., Sandberg A. A. Gardner syndrome in a man with an interstitial deletion of 5q. Am J Med Genet. 1986 Nov;25(3):473–476. doi: 10.1002/ajmg.1320250309. [DOI] [PubMed] [Google Scholar]
- Hollstein M. C., Metcalf R. A., Welsh J. A., Montesano R., Harris C. C. Frequent mutation of the p53 gene in human esophageal cancer. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9958–9961. doi: 10.1073/pnas.87.24.9958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hollstein M. C., Smits A. M., Galiana C., Yamasaki H., Bos J. L., Mandard A., Partensky C., Montesano R. Amplification of epidermal growth factor receptor gene but no evidence of ras mutations in primary human esophageal cancers. Cancer Res. 1988 Sep 15;48(18):5119–5123. [PubMed] [Google Scholar]
- Jiang W., Kahn S. M., Guillem J. G., Lu S. H., Weinstein I. B. Rapid detection of ras oncogenes in human tumors: applications to colon, esophageal, and gastric cancer. Oncogene. 1989 Jul;4(7):923–928. [PubMed] [Google Scholar]
- Joslyn G., Carlson M., Thliveris A., Albertsen H., Gelbert L., Samowitz W., Groden J., Stevens J., Spirio L., Robertson M. Identification of deletion mutations and three new genes at the familial polyposis locus. Cell. 1991 Aug 9;66(3):601–613. doi: 10.1016/0092-8674(81)90022-2. [DOI] [PubMed] [Google Scholar]
- Kinzler K. W., Nilbert M. C., Su L. K., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hedge P., McKechnie D. Identification of FAP locus genes from chromosome 5q21. Science. 1991 Aug 9;253(5020):661–665. doi: 10.1126/science.1651562. [DOI] [PubMed] [Google Scholar]
- Kinzler K. W., Nilbert M. C., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hamilton S. R., Hedge P., Markham A. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science. 1991 Mar 15;251(4999):1366–1370. doi: 10.1126/science.1848370. [DOI] [PubMed] [Google Scholar]
- Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee J. H., Kavanagh J. J., Wildrick D. M., Wharton J. T., Blick M. Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas. Cancer Res. 1990 May 1;50(9):2724–2728. [PubMed] [Google Scholar]
- Leppert M., Dobbs M., Scambler P., O'Connell P., Nakamura Y., Stauffer D., Woodward S., Burt R., Hughes J., Gardner E. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science. 1987 Dec 4;238(4832):1411–1413. doi: 10.1126/science.3479843. [DOI] [PubMed] [Google Scholar]
- Lu S. H., Hsieh L. L., Luo F. C., Weinstein I. B. Amplification of the EGF receptor and c-myc genes in human esophageal cancers. Int J Cancer. 1988 Oct 15;42(4):502–505. doi: 10.1002/ijc.2910420406. [DOI] [PubMed] [Google Scholar]
- MacDonald W. C., MacDonald J. B. Adenocarcinoma of the esophagus and/or gastric cardia. Cancer. 1987 Sep 1;60(5):1094–1098. doi: 10.1002/1097-0142(19870901)60:5<1094::aid-cncr2820600529>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
- Meltzer S. J., Mane S. M., Wood P. K., Resau J. H., Newkirk C., Terzakis J. A., Korelitz B. I., Weinstein W. M., Needleman S. W. Activation of c-Ki-ras in human gastrointestinal dysplasias determined by direct sequencing of polymerase chain reaction products. Cancer Res. 1990 Jun 15;50(12):3627–3630. [PubMed] [Google Scholar]
- Meltzer S. J., Yin J., Huang Y., McDaniel T. K., Newkirk C., Iseri O., Vogelstein B., Resau J. H. Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4976–4980. doi: 10.1073/pnas.88.11.4976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morita R., Ishikawa J., Tsutsumi M., Hikiji K., Tsukada Y., Kamidono S., Maeda S., Nakamura Y. Allelotype of renal cell carcinoma. Cancer Res. 1991 Feb 1;51(3):820–823. [PubMed] [Google Scholar]
- Morita R., Saito S., Ishikawa J., Ogawa O., Yoshida O., Yamakawa K., Nakamura Y. Common regions of deletion on chromosomes 5q, 6q, and 10q in renal cell carcinoma. Cancer Res. 1991 Nov 1;51(21):5817–5820. [PubMed] [Google Scholar]
- Nakamura Y., Lathrop M., Leppert M., Dobbs M., Wasmuth J., Wolff E., Carlson M., Fujimoto E., Krapcho K., Sears T. Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet. 1988 Nov;43(5):638–644. [PMC free article] [PubMed] [Google Scholar]
- Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A., Koyama K., Utsunomiya J., Baba S., Hedge P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991 Aug 9;253(5020):665–669. doi: 10.1126/science.1651563. [DOI] [PubMed] [Google Scholar]
- Palau F., Prieto F., Badia L., Beneyto M., Benet I. Chromosome 5 abnormalities in acute lymphoblastic leukemia. Cancer Genet Cytogenet. 1991 Apr;52(2):173–179. doi: 10.1016/0165-4608(91)90460-c. [DOI] [PubMed] [Google Scholar]
- Radice P., Pierotti M. A., Lacerenza S., Mondini P., Radice M. T., Pilotti S., Della Porta G. Loss of heterozygosity in human germinal tumors. Cytogenet Cell Genet. 1989;52(1-2):72–76. doi: 10.1159/000132843. [DOI] [PubMed] [Google Scholar]
- Reid B. J., Haggitt R. C., Rubin C. E., Rabinovitch P. S. Barrett's esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma. Gastroenterology. 1987 Jul;93(1):1–11. [PubMed] [Google Scholar]
- Sano T., Tsujino T., Yoshida K., Nakayama H., Haruma K., Ito H., Nakamura Y., Kajiyama G., Tahara E. Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas. Cancer Res. 1991 Jun 1;51(11):2926–2931. [PubMed] [Google Scholar]
- Sato T., Tanigami A., Yamakawa K., Akiyama F., Kasumi F., Sakamoto G., Nakamura Y. Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. Cancer Res. 1990 Nov 15;50(22):7184–7189. [PubMed] [Google Scholar]
- Solomon E., Voss R., Hall V., Bodmer W. F., Jass J. R., Jeffreys A. J., Lucibello F. C., Patel I., Rider S. H. Chromosome 5 allele loss in human colorectal carcinomas. Nature. 1987 Aug 13;328(6131):616–619. doi: 10.1038/328616a0. [DOI] [PubMed] [Google Scholar]
- Tsuda T., Nakatani H., Matsumura T., Yoshida K., Tahara E., Nishihira T., Sakamoto H., Yoshida T., Terada M., Sugimura T. Amplification of the hst-1 gene in human esophageal carcinomas. Jpn J Cancer Res. 1988 May;79(5):584–588. doi: 10.1111/j.1349-7006.1988.tb00026.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsutsumi M., Sakamoto H., Yoshida T., Kakizoe T., Koiso K., Sugimura T., Terada M. Coamplification of the hst-1 and int-2 genes in human cancers. Jpn J Cancer Res. 1988 Apr;79(4):428–432. doi: 10.1111/j.1349-7006.1988.tb01609.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Victor T., Du Toit R., Jordaan A. M., Bester A. J., van Helden P. D. No evidence for point mutations in codons 12, 13, and 61 of the ras gene in a high-incidence area for esophageal and gastric cancers. Cancer Res. 1990 Aug 15;50(16):4911–4914. [PubMed] [Google Scholar]
- Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
- Wagata T., Ishizaki K., Imamura M., Shimada Y., Ikenaga M., Tobe T. Deletion of 17p and amplification of the int-2 gene in esophageal carcinomas. Cancer Res. 1991 Apr 15;51(8):2113–2117. [PubMed] [Google Scholar]
- Wang H. H., Antonioli D. A., Goldman H. Comparative features of esophageal and gastric adenocarcinomas: recent changes in type and frequency. Hum Pathol. 1986 May;17(5):482–487. doi: 10.1016/s0046-8177(86)80038-7. [DOI] [PubMed] [Google Scholar]
- Yamamoto T., Kamata N., Kawano H., Shimizu S., Kuroki T., Toyoshima K., Rikimaru K., Nomura N., Ishizaki R., Pastan I. High incidence of amplification of the epidermal growth factor receptor gene in human squamous carcinoma cell lines. Cancer Res. 1986 Jan;46(1):414–416. [PubMed] [Google Scholar]
- Yokota J., Tsukada Y., Nakajima T., Gotoh M., Shimosato Y., Mori N., Tsunokawa Y., Sugimura T., Terada M. Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix. Cancer Res. 1989 Jul 1;49(13):3598–3601. [PubMed] [Google Scholar]
- Yokota J., Wada M., Shimosato Y., Terada M., Sugimura T. Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9252–9256. doi: 10.1073/pnas.84.24.9252. [DOI] [PMC free article] [PubMed] [Google Scholar]