Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients

Yasuo Miyoshi, Hiroshi Ando, Hiroki Nagase, Isamu Nishisho, Akira Horii, Yoshio Miki, Takesada Mori, Joji Utsunomiya, Shozo Baba, Gloria M Petersen, Stanley R. Hamilton, Kenneth W. Kinzler, Bert Vogelstein, Yusuke Nakamura

Research output: Contribution to journalArticle

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Abstract

We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5′ half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis.

Original languageEnglish (US)
Pages (from-to)4457-4461
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number10
StatePublished - 1992
Externally publishedYes

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APC Genes
Adenomatous Polyposis Coli
Germ-Line Mutation
Mutation
Point Mutation
Terminator Codon
Genetic Counseling
Missense Mutation
Ribonucleases
Base Pairing
Exons
Polymerase Chain Reaction
DNA
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Miyoshi, Y., Ando, H., Nagase, H., Nishisho, I., Horii, A., Miki, Y., ... Nakamura, Y. (1992). Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proceedings of the National Academy of Sciences of the United States of America, 89(10), 4457-4461.

Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. / Miyoshi, Yasuo; Ando, Hiroshi; Nagase, Hiroki; Nishisho, Isamu; Horii, Akira; Miki, Yoshio; Mori, Takesada; Utsunomiya, Joji; Baba, Shozo; Petersen, Gloria M; Hamilton, Stanley R.; Kinzler, Kenneth W.; Vogelstein, Bert; Nakamura, Yusuke.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 10, 1992, p. 4457-4461.

Research output: Contribution to journalArticle

Miyoshi, Y, Ando, H, Nagase, H, Nishisho, I, Horii, A, Miki, Y, Mori, T, Utsunomiya, J, Baba, S, Petersen, GM, Hamilton, SR, Kinzler, KW, Vogelstein, B & Nakamura, Y 1992, 'Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 10, pp. 4457-4461.
Miyoshi, Yasuo ; Ando, Hiroshi ; Nagase, Hiroki ; Nishisho, Isamu ; Horii, Akira ; Miki, Yoshio ; Mori, Takesada ; Utsunomiya, Joji ; Baba, Shozo ; Petersen, Gloria M ; Hamilton, Stanley R. ; Kinzler, Kenneth W. ; Vogelstein, Bert ; Nakamura, Yusuke. / Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 10. pp. 4457-4461.
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