1993 Fiscal Year Annual Research Report

高発がん家系の解析

Research Project

Project/Area Number	05151050
Research Institution	Kyushu University
Principal Investigator	笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
Co-Investigator(Kenkyū-buntansha)	江見充癌研究会, 癌研究所, 研究員 (90221118) 小川浩愛知みずほ大学, 人間科学部, 教授 (80073138) 有吉寛愛知がんセンター, 部長 (50151189) 馬場正三浜松医科大学, 医学部, 教授 (40107818) 佐々木正夫京都大学, 放射線生物研究センター, 教授 (20013857)
Keywords	高発がん家系 / 乳がん / MDC遺伝子 / APC遺伝子 / P53遺伝子
Research Abstract	発がんの遺伝的制御機構を明らかにする目的で、我国における高発がん家系の実態調査、検体収集ならびに家族性家系大腸ポリポーシスおよび乳がんを対象とした遺伝子解析を行った。日本における小児がん登録を調査し、先天異常を伴う小児がん症例について試料提供に関するアンケート調査を行い、先天異常合併例および家族歴陽性例の検体収集体制を整えた。一方、成人がん登録の調査により、全症例の約0.3%が高発がん家系由来であることを示し、このうち胃がんを多発する家系内の胃がん、肺小細胞がんを合併した症例でp53ゲノム遺伝子変異を検出した。一方、高発がん家系を対象としたがん組織および家族を含めた血液試料の収集を行っている。家族性大腸ポリポーシスにおけるAPC遺伝子変異の位置と臨床像との比較検討から、眼底色素沈着を伴う症例では577〜1309コドンの変異を有することを明らかにした。乳がん細胞のクロナリティをX染色体のメチル化を指標に検討した結果、前がん病変および乳がん組織とも起源が単一細胞と考えられることが明らかになった。一方、乳がんあるいは卵巣がんにおける第17染色体長腕のヘテロ接合性を検討し、それぞれの約40%に欠失が認められるが、その共通領域は17q21.3と17q25.1〜q25.3の2箇所であることを明らかにした。さらに17q21.3領域の構造をコスミドマーカーを用いて詳細に検討し、乳がん650例中の2例において、サザン法で再構成・増幅異常を示す領域を同定し、ここに新しい遺伝子(MDC遺伝子)を見出した。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Shirasawa S: "Altered growth of human colon cancer cell lines disrupted at activated k-ras" Science. 260. 85-88 (1993)
[Publications] Emi M: "A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers" Nature Genet.5. 151-157 (1993)
[Publications] Ando H: "Detection of 12 germ-line mutations in the adenomatous polyposis coli gene by polymerase chain reaction" Gastroenterology. 104. 989-993 (1993)
[Publications] Emi M: "A primary genetic linkage map of 14 polymorphic loci for the short arm of human chromosome 8" Genomics. 15. 530-534 (1993)
[Publications] Fujiwara Y: "Frequent multiplication of the long arm of chromosome 8 in hepatocellular carcinoma" Cancer Res.53. 857-860 (1993)
[Publications] Fujiwara Y: "Evidence for a presence of two tumor suppressor genes on chromosome 8p for colorectal carcinoma" Cancer Res.53. 1172-1174 (1993)
[Publications] Noguchi S: "Clonal analysis of fibroadenoma and phyllodes tumor of the breast" Cancer Res.53. 4071-4074 (1993)
[Publications] Matsui I: "Neurofibromatosis type 1 and childhood cancer" Cancer. 72. 2746-2754 (1993)
[Publications] Habuchi T: "Influence of cigarette smoking and schistosomiasis on p53 gene mutation in urothelial cancer" Cancer Res.53. 3795-3799 (1993)
[Publications] Habuchi T: "Metachronous multifocal development of urothelial cancers by intraluminal seeding:evidence by p53 mutationanalysis" Lancet. 1087-1088 (1993)
[Publications] Inagaki T: "Establishiment of human oral-cancer cell lines(kosc-2 and 3)carrying p53 and C-myc abnormalities by geneticin treatment" Int.J.Cancer. 56. 1-8 (1993)
[Publications] Nakamura S: "Nuclear DNA content of isolated crypts of background colonic mucosa from patients with familial adenomatous polyposis and sporadic coloreatal cancer" Gut. 34. 1240-1244 (1993)
[Publications] Noguchi S: "Preoperative discrimination of fibroadcnoma which is clincally and cytologically indistinguishable from breast carcinoma by clonal analysis of fine needle aspirates" Breast Cancer. in press.
[Publications] Noguchi S: "Clonal analysis of predominantly intraductal carcinoma and precanccrous lesions of the breast by means of polymerase chain reaction" Cancer Res.in press.
[Publications] Noguchi S: "Discrimination of primary and secondary breast cancer by clonal analysis" Surgery. in press.

1993 Fiscal Year Annual Research Report

高発がん家系の解析

Principal Investigator

笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)

Research Products

[Publications] Shirasawa S: "Altered growth of human colon cancer cell lines disrupted at activated k-ras" Science. 260. 85-88 (1993)

[Publications] Emi M: "A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers" Nature Genet.5. 151-157 (1993)

[Publications] Ando H: "Detection of 12 germ-line mutations in the adenomatous polyposis coli gene by polymerase chain reaction" Gastroenterology. 104. 989-993 (1993)

[Publications] Emi M: "A primary genetic linkage map of 14 polymorphic loci for the short arm of human chromosome 8" Genomics. 15. 530-534 (1993)

[Publications] Fujiwara Y: "Frequent multiplication of the long arm of chromosome 8 in hepatocellular carcinoma" Cancer Res.53. 857-860 (1993)

[Publications] Fujiwara Y: "Evidence for a presence of two tumor suppressor genes on chromosome 8p for colorectal carcinoma" Cancer Res.53. 1172-1174 (1993)

[Publications] Noguchi S: "Clonal analysis of fibroadenoma and phyllodes tumor of the breast" Cancer Res.53. 4071-4074 (1993)

[Publications] Matsui I: "Neurofibromatosis type 1 and childhood cancer" Cancer. 72. 2746-2754 (1993)

[Publications] Habuchi T: "Influence of cigarette smoking and schistosomiasis on p53 gene mutation in urothelial cancer" Cancer Res.53. 3795-3799 (1993)

[Publications] Habuchi T: "Metachronous multifocal development of urothelial cancers by intraluminal seeding:evidence by p53 mutationanalysis" Lancet. 1087-1088 (1993)

[Publications] Inagaki T: "Establishiment of human oral-cancer cell lines(kosc-2 and 3)carrying p53 and C-myc abnormalities by geneticin treatment" Int.J.Cancer. 56. 1-8 (1993)

[Publications] Nakamura S: "Nuclear DNA content of isolated crypts of background colonic mucosa from patients with familial adenomatous polyposis and sporadic coloreatal cancer" Gut. 34. 1240-1244 (1993)

[Publications] Noguchi S: "Preoperative discrimination of fibroadcnoma which is clincally and cytologically indistinguishable from breast carcinoma by clonal analysis of fine needle aspirates" Breast Cancer. in press.

[Publications] Noguchi S: "Clonal analysis of predominantly intraductal carcinoma and precanccrous lesions of the breast by means of polymerase chain reaction" Cancer Res.in press.

[Publications] Noguchi S: "Discrimination of primary and secondary breast cancer by clonal analysis" Surgery. in press.

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)