Summary
DNA technology using DNA sequence polymorphisms has brought a new system to the fields of medicine and forensic science, especially for the studies of genetic diseases and tumor suppressor genes, and for identification of individuals for forensic purposes. Linkage analysis based on segregation of polymorphic alleles in affected families has contributed to identification of many genetic diseases. We isolated a large number of polymorphic DNA markers, called VNTR (variable number of tandem repeat) markers and identified the APC gene that is responsible for familial adenomatous polyposis (FAP) by means of a so-called “positional cloning” and characterized germline and somatic mutations of the APC gene in colorectal cancer patients. In addition, we have applied genetic information during colorectal carcinogenesis to sensitive diagnosis of lymph-node metastasis of colorectal cancer.
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Aoki T, Mori T, XiQun D, Nishihira T, Matsubara T, Nakamura Y (1994): Allelotype study of esophageal carcinoma. Genes Chromosomes Cancer10: 177–182
Ariyama T, Inazawa J, Ezaki T, Nakamura Y, Horii A, Abe T (1995): High-resolution cytogenetic mapping of the short arm of chromosome 1 with newly isolated 411 cosmid markers by fluorescencein situ hybridization: the precise order of 18 markers on 1p36.1 on prophase chromosomes and “stretched” DNAs. Genomics25: 114–123
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 (London)328: 614–616
Emi M, Koyama K, Okui K, Takahashi E, Oshimura M, Nakamura Y (1992): Isolation and mapping of 88 new RFLP markers on human chromosome 8. Genomics13: 1261–1266
Fujimori M, Tokino T, Hino O, Kitagawa T, Imamura T, Okamoto E, Mitsunobu M, Ishikawa T, Nakagama H, Harada H, Yagura M, Matsubara K, Nakamura Y (1991): Allelotype study of primary hepatocellular carcinoma. Cancer Res51: 89–93
Gatti R, Nakamura Y, Nussmeier M, Susi E, Shan W, Grody W (1989): Informativeness of VNTR genetic markers for detecting chimerism after bone marrow transplantation. Dis Markers7: 105–112
Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M, Sargeant L, Krapcho K, Wolff E, Burt R, Hughes JP, Warrington J, McPherson J, Wasmuth J, Paslier DL, Abderrahim H, Cohen D, Leppert M, White R (1991): Identification and characterization of the familial adenomatous polyposis coli gene. Cell66: 589–600
Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millasseau P, Marc S, Bernardi G, Lathrop M, Weissenbach J (1994): The 1993–1994 Genethon human genetic linkage map. Nature Genet7: 246–339
Hayashi N, Ito I, Yanagisawa A, Kato Y, Nakamori S, Imaoka S, Watanabe H, Ogawa M, Nakamura Y (1995): Genetic diagnosis of lymph-node metastasis allows accurate prognosis of patients with colorectal cancer. Lancet345: 1257–1259
Herrera L, Kakati S, Gibas L, Pietrzak E, Sandberg AA (1986): Gardner syndrome in a man with an interstitial deletion of 5q. Am J Med Genet25: 473–476
Hori T, Takahashi E, Tanigami A, Tokino T, Nakamura Y (1992): A high-resolution cytogenetic map of 168 cosmid DNA markers for human chromosome 11. Genomics13: 129–133
Horii A, Nakatsuru S, Miyoshi Y, Ichii S, Nagase H, Kato Y, Yanagisawa A, Nakamura Y (1992a): The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer. Cancer Res52: 3231–3233
Horii A, Nakatsuru S, Miyoshi Y, Ichii S, Nagase H, Ando H, Yanagisawa A, Tsuchiya E, Kato Y, Nakamura Y (1992b): Frequent somatic mutation of the APC gene in human pancreatic cancer. Cancer Res52: 6696–6698
Horii A, Nakatsuru S, Ichii S, Nagase H, Nakamura Y (1993): Multiple forms of the APC gene transcripts and their tissue-specific expression. Hum Mol Genet2: 283–287, 1993
Ichii S, Horii A, Nakatsuru S, Furuyama J, Utsunomiya J, Nakamura Y (1992): Inactivation of both APC alleles in an early stage of colon adenomas in a patient with familial adenomatous polyposis (FAP). Hum Mol Genet1: 387–390
Ichii S, Takeda S, Horii A, Nakatsuru S, Miyoshi Y, Emi M, Fujiwara Y, Koyama K, Furuyama J, Utsunomiya J, Nakamura Y (1993): Detailed analysis of genetic alterations in colorectal tumors from patients with and without familial adenomatous polyposis (FAP). Oncogene8: 2399–2405
Inazawa J, Saito H, Ariyama T, Abe T, Nakamura Y (1993): High-resolution cytogenetic mapping of 342 new cosmid markers on human chromosome 17 by fluorescentin situ hybridization. Genomics17: 153–162
Joslyn G, Carlson M, Thliveris A, Albertsen H, Gelbert L, Samowitz W, Groden J, Stevens J, Spirio L, Robertson M, Sargeant L, Krapcho K, Wolff E, Burt R, Hughes JP, Warrington J, McPherson J, Wasmuth J, Paslier DL, Abderrahim H, Cohen D, Leppert M, White R (1991): Identification of deletion mutations and three new genes at the familial polyposis locus. Cell66: 601–613
Julier C, Nakamura Y, Lathrop M, O'Connell P, Leppert M, Mohandas T, Lalouel J-M, White R (1990a): A primary map of 24 loci on human chromosome 16. Genomics6: 419–427
Julier C, Nakamura Y, Lathrop M, O'Connell P, Leppert M, Litt M, Mohandas T, Lalouel J-M, White R (1990b): A detailed genetic map of the long arm of chromosome 11. Genomics7: 335–345
Kasai K, Nakamura Y, White R (1990): Amplification of a VNTR locus (pMCT118) by the polymerase chain reaction (PCR) and its application to forensic science. J Forensic Sci35: 1196–1200
Kinzler KW, Nilbert MC, Su L, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, Finniear R, Markham A, Groffen J, Boguski MS, Alschul SF, Horii A, Ando H, Miyoshi Y, Miki Y, Nishisho I, Nakamura Y (1991): Identification of FAP locus genes from chromosome 5q21. Science253: 661–665
Lathrop M, Nakamura Y, Cartwright P, O'Connell P, Leppert M, Jones C, Tateishi H, Bragg T, Lalouel J-M, White R (1988a): A primary genetic map of markers for human chromosome 10. Genomics2: 157–164
Lathrop M, Nakamura Y, O'Connell P, Leppert M, Woodward S, Lalouel J-M, White R (1988b): A mapped set of genetic markers for human chromosome 9. Genomics3: 361–366
Lathrop M, O'Connell P, Leppert M, Nakamura Y, Farrall M, Tsui L-C, Lalouel J-M, White R (1989): Twenty-five loci form a continuous linkage map of markers for human chromosome 7. Genomics5: 866–873
Leppert M, Dobbes M, Scambler P, O'Connell P, Nakamura Y, Stauffer D, Woodward S, Burt R, Hughes J, Gardner E, Lathrop M, Wasumuth J, Lalouel J-M, White R (1987): The gene for familial polyposis coli maps to the long arm of chromosome 5. Science238: 1411–1413
Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler K, Vogelstein B, Nakamura Y (1992): Disruption of the APC gene by retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res52: 643–645
Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, Aoki T, Miki Y, Mori T, Nakamura Y (1992): Somatic mutation of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet1: 229–233
Morita R, Ishikawa J, Tsutsumi M, Hikiji K, Tsukada Y, Kamidono S, Maeda S, Nakamura Y (1991): Allelotype of renal cell carcinoma. Cancer Res51: 820–823
Nagase H, Miyoshi Y, Horii A, Aoki T, Ogawa M, Utsunomiya J, Baba S, Sasazuki T, Nakamura Y (1992a): Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis (FAP) patients. Cancer Res52: 4055–4057
Nagase H, Miyoshi Y, Horii A, Aoki T, Petersen GM, Vogelstein B, Maher E, Ogawa M, Utsunomiya J, Baba S, Nakamura Y (1992b): Screening for germ-line mutations in familial adenomatous polyposis (FAP) patients: 61 new patients and a summary of 150 unrelated patients. Hum Mutat1: 467–473
Nagase H, Miyoshi Y, Horii A, Aoki T, Petersen GM, Vogelstein B, Maher E, Ogawa M, Utsunomiya J, Baba S, Nakamura Y (1992b): Screening for germ-line mutations in familial adenomatous polyposis (FAP) patients: 61 new patients and a summary of 150 unrelated patients. Hum Mutat1: 467–473
Nagase H, Nakamura Y (1993): Mutations of the APC (adenomatous polyposis coli) gene. Hum Mutat2: 425–434
Nakamura Y, Leppert M, O'Connell P, Wolff R, Holm T, Culver M, Martin C, Fujimoto E, Hoff M, Kumlin E, White R (1987): Variable Number of Tandem Repeat (VNTR) markers for human gene mapping. Science235: 1616–1622
Nakamura Y, Carlson M, Krapcho K, Kanamori M, White R (1988a): A new approach for isolating VNTR markers. Am J Hum Genet43: 854–859
Nakamura Y, Lathrop M, O'Connell P, Leppert M, Barker D, Wright E, Skolnick M, Kondoleon S, Litt M, Lalouel J-M, White R (1988b): A mapped set of DNA markers for human chromosome 17. Genomics2: 302–307
Nakamura Y, Lathrop M, O'Connell P, Leppert M, Lalouel J-M, White R (1988c): A primary map of 10 DNA markers and 2 serological markers for human chromosome 19. Genomics2: 67–71
Nakamura Y, Lathrop M, O'Connell P, Leppert M, Lalouel J-M, White R (1988d): A mapped set of markers for human chromosome 15. Genomics3: 342–346
Nakamura Y, Lathrop M, Bragg T, Jones C, O'Connell P, Leppert M, Lalouel J-M, White R (1988e): An extended linkage map for human chromosome 10. Genomics3: 389–392
Nakamura Y, Lathrop M, Leppert M, Dobbes M, Wasumuth J, Wolff E, Carlson M, Fujimoto E, Krapcho K, Woodward S, Burt R, Hughes J, Gardner E, Lalouel J-M, White R (1988f): Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet43: 638–644, 1988
Nakamura Y, Lathrop M, O'Connell P, Leppert M, Lalouel J-M, White R (1989a): Frequent recombination was observed in the distal end of the long arm of human chromosome 14. Genomics4: 76–81
Nakamura Y, Leppert M, O'Connell P, Lathrop M, Lalouel J-M, White R (1989b): A genetic linkage map of markers for human chromosome 20. Genomics5: 945–947
nakamura Y (1993): The role of the APC (adenomatous polyposis coli) gene in human cancers. Adv Cancer Genet62: 65–87
Nakamura Y, Okui K, Takahashi E, Koyama K (1994): Isolation and mapping of 328 new cosmid markers on human chromosome 8: construction of a high resolution cytogenetic map of chromosome 8 with 416 markers. Cytogenet Cell Genet65: 115–118
Nakatsuru S, Yanagisawa A, Ichii S, Tahara E, Kato Y, Nakamura Y, Horii A (1992): Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma. Hum Mol Genet1: 559–563
NIH/CEPH Collaborative Mapping Group (1992): A comprehensive genetic linkage map of the human genome. Science258: 67–86
Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P, Markham A, Krush AJ, Petersen G, Hamilton SR, Nilbert MC, Levy DB, Bryan TM, Preisinger AC, Smith KJ, Su L, Kinzler KW, Vogelstein B (1991): Mutations of chromosome 5q21 genes in fAP and colorectal cancer patients. Science253: 665–669
O'Connell P, Lathrop M, Leppert M, Nakamura Y, Muller U, Lalouel J-M, White R (1989a): Twelve loci form a continuous linkage map for human chromosome 18. Genomics3: 367–372
O'Connell P, Lathrop M, Nakamura Y, Leppert M, Ardinger RH, Murray JL, Lalouel J-M, White R (1989b): Twenty-eight loci form a continuous linkage map of markers for human chromosome 1. Genomics4: 12–20
O'Connell P, Lathrop M, Nakamura Y, Leppert M, Lalouel J-M, White R (1989c): Twenty loci form a continuous linkage map of markers for human chromosome 2. Genomics5: 738–745
Odelberg SJ, Plaetke R, Eldridge JR, Ballard L, O'Connell P, Nakamura Y, Leppert M, Lalouel J-M, White R (1989): Characterization of VNTR loci by high-resolution agarose gel electrophoresis: implications for parentage testing and forensic individualization. Genomics5: 915–924
Sato T, Saito H, Morita R, Koi S, Lee JH, Nakamura Y (1991a): Allelotype of human ovarian cancer. Cancer Res51: 5118–5121
Sato T, Akiyama F, Sakamoto G, Kasumi F, Nakamura Y (1991b): Accumulation of geneti alterations and progression of primary breast cancer. Cancer Res51: 5794–5799
Takahashi E, Yamakawa K, Nakamura Y, Hori T (1992): A high resolution cytogenetic map of human chromosome 3: localization of 292 new cosmid markers by a direct mapping system with fluorescencein situ hybridization. Genomics13: 1047–1055
Takahashi E, Hitomi S, Koyama K, Nakamura Y (1993a): A high-resolution cytogenetic map of human chromosome 5: localization of 206 new cosmid markers by direct R-banding fluorescencein situ hybridization. Genomics17: 234–236
Takahashi E, Koyama K, Hitomi S, Nakamura Y (1993b): A high-resolution cytogenetic map of human chromosome 12: localization of 195 new cosmid markers by direct R-banding fluorescencein situ hybridization. Hum Genet92: 405–409
Takahashi E, Koyama K, Hitomi A, Itoh H, Nakamura Y (1994a): A high-resolution cytogenetic map of human chromosome 9: localization of 203 new cosmid markers by direct R-banding fluorescencein situ hybridization. Genomics19: 373–375
Takahashi E, Koyama K, Hirai M, Itoh H, Nakamura Y (1994b): A high-resolution cytogenetic map of human chromosome 2: localization of 434 cosmid markers by direct R-banding fluorescencein situ hybridization. Cytogenet Cell Genet68: 112–114
Tsuchiya E, Nakamura Y, Weng S, Nakagawa K, Tsuchiya S, Sugano H, Kitagawa T (1992): Allelotype of non-small cell lung carcinoma-comparison of loss of heterozygosity between squamous cell carcinoma and adenocarcinoma. Cancer Res52: 2478–2481
White R, Lalouel J-M, Leppert M, Lathrop M, Nakamura Y, O'Connell P (1989): Linkage maps of human chromosomes. Genome31: 1066–1072
Yamakawa K, Takahashi E, Saito H, Sato T, Oshimura M, Hori T, Nakamura Y (1991a): Isolation and mapping of 75 new DNA markers on human chromosome 3. Genomics9: 536–543
Yamakawa K, Morita R, Takahashi E, Lathrop M, Nakamura Y (1991b): A genetic linkage map of 41 RFLP markers for human chromosome 3. Genomics11: 565–572
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Nakamura, Y. Application of DNA markers to clinical genetics. Jap J Human Genet 41, 1–10 (1996). https://doi.org/10.1007/BF01892620
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DOI: https://doi.org/10.1007/BF01892620