1998 Fiscal Year Annual Research Report

ヒト癌の発生,伸展に関与する遺伝子異常の解析

Research Project

Project/Area Number	07272204
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (A)
Research Institution	Tohoku University
Principal Investigator	堀井明東北大学, 医学部, 教授 (40249983)
Keywords	癌抑制遺伝子 / 膵癌 / 子宮内膜癌 / 肺癌 / 腎癌 / DNAミスマッチ修復異常 / DUSP6遺伝子 / H-cadherin遺伝子
Research Abstract	1. 膵癌に関しては,6q,12qにおける共通欠失領域を特定し,YAC,BACによるコンティグを成,さらに発現している遺伝子のスクリーニングを行った。12qにおいては2個の候補遺伝子にいて異常の有無を調べたが,構造異常は見られなかった。尚,12q21のDUSP6遺伝子では,多の膵癌細胞株で発現の減弱や消失が観察されたため,現在,発癌との関連についてさらなる検討を加えている。また,膵液中の細胞を用い,膵癌で高頻度に検出されている9p,17p,18qの欠層と8q,20qの増幅を指標にFISHによる診断を試みた結果,FISH法が非常に有効であり,かつ8qの欠失がこれらの領域の中でもっとも初期に生じている異常であることを明らかにした。 2. 子宮内膜癌については,前年度までに10q25-q26に同定した染色体欠失領域を100-kbに特定した。さらに,この領域の欠失は子宮内膜異型増殖症においても高頻度に見られ,10q25-q26の欠失が子宮内膜の発癌過程における初期変化であり,かつ子宮内膜異型増殖症が前癌病変であることが示唆された。また,子宮内膜異型増殖症においてDNAミスマッチ修復異常の関与も高頻度であり,BAX遺伝子,IGFIIR遺伝子,PTEN遺伝子にも異常が生じていることを明らかにした。 3. 肺癌において,16q24に狭い範囲の高頻度欠失を検出した。16q24にはH-cadherin遺伝子が存在するので,さらなる検討を加えた結果,高頻度にこの遺伝子の発現が消失しており,また,定現が消失した腫瘍ではプロモーター領域の高頻度のメチル化を明らかにした。尚,胃癌でもこの領域にLOHが検出されたが,H-cadherin遺伝子の異常の関与を示唆する結果は得られなかった。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Sato,M.: "Identification of a 910-kb region of common alletic loss in chromosome bands 16q24.1-q24.2 in human lung cancer." Genes Chromosomes Cancer. 22. 1-8 (1998)
[Publications] Orikasa,K.: "Identification of a 700 kb region of common allelic loss in chromosome bands 3p14.3-p21.1 in human renal cell carcinoma." Gencer Genetics and Cytogenetics. 104. 104-110 (1998)
[Publications] Wakatsuki,S.: "Adrenocortical tumor in a patient with familial adenomatous polyposis:A case associated with a complete inactivating mutation of the APC gene and unusual histological features." Human Pathology. 29. 302-306 (1998)
[Publications] Yamakawa,H.: "Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer." Genes,Chromosomes & Cancer. 23. 74-77 (1998)
[Publications] Ouyang,H.: "The BAX gene,the promoter of apoptosis,mutated in genetically unstable cancers of the colorectum,stomach,and genetically unstable cancers of the colorectum,stomach,and endometrium." Clinical Cancer Research. 4. 1071-1074 (1998)
[Publications] Kimura,M.: "Identification of two common regions of allelic loss in chromosome arm 12q in human panecrcatic cancer." Cancer Research. 4. 2456-2460 (1998)
[Publications] Matsuzaki,M.: "Detailed deletion mapping on chromosome 1p32-p56 in human colorectal cancer:Identification of three distinct regions of common allelic loss." International Journal of Oncology. 13. 1229-1233 (1998)
[Publications] Sato,M.: "The H-cadherin(CDH13)gene is inactivated in human lung cancer." Human Genetics. 103. 96-101 (1998)
[Publications] Sato,M.: "Chromosome bands 3p14.2,9p21,and 13q14 are mequently deleted in roentgenographically occult bronchogenic squamous cell carcinoma of the lung." Genes,Chromosomes & Cancer. 23. 367-370 (1998)
[Publications] Furukawa,T.: "Genomic analysis of DUSP6,a dual specificity MAP kinase phosphatase,in pancreatic cancer." Cytogenetics and Cell Genetics. 82. 156-159 (1998)
[Publications] Orikasa,K.: "Infrequent genetic altertions of the PTEN gene in Japanese patients with sporadic prostate cancer." Journal of Human Genetics. 43. 228-230 (1998)
[Publications] Fukushige,S.: "Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis." Cancer Research. 58. 4222-4226 (1998)
[Publications] Sato,M.: "A GT dinucleotide repeat polymorpnism in intron 1 of the Hcadherin(CDH13)gene." Journal of Human Genetics. 43. 285-286 (1998)
[Publications] Yoshinaga,K.: "The PTEN,BAX,and IGFIIR genes are mutated in endometria atypical hyperplasia." Japanese Journal of Cancer Research. 89. 985-990 (1998)
[Publications] Yatsuoka,T.: "Genomic analysis of the thymine DNA glycosylase(TDG)gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma." International Journal of Pancreatology. (in press).
[Publications] Mori,Y.: "Chromosome band 16q24 is frequently deleted in human gastric cancer." British Journal of Cancer. (in press).
[Publications] Abe,T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer." Genes,Chromosomes & Cancer. (in press).
[Publications] Han,S.,: "Infrequent somatic mutations of the p73 gene in various human cancers." European Journal of Surgical Oncology. (in press).
[Publications] Kondo,E.: "The human PMS2L proteins do not interact with hMLH,a major DNA mismatch repair protein." Journal of Biochemistry. (in press).

1998 Fiscal Year Annual Research Report

ヒト癌の発生,伸展に関与する遺伝子異常の解析

Principal Investigator

堀井 明 東北大学, 医学部, 教授 (40249983)

Research Products

[Publications] Sato,M.: "Identification of a 910-kb region of common alletic loss in chromosome bands 16q24.1-q24.2 in human lung cancer." Genes Chromosomes Cancer. 22. 1-8 (1998)

[Publications] Orikasa,K.: "Identification of a 700 kb region of common allelic loss in chromosome bands 3p14.3-p21.1 in human renal cell carcinoma." Gencer Genetics and Cytogenetics. 104. 104-110 (1998)

[Publications] Wakatsuki,S.: "Adrenocortical tumor in a patient with familial adenomatous polyposis:A case associated with a complete inactivating mutation of the APC gene and unusual histological features." Human Pathology. 29. 302-306 (1998)

[Publications] Yamakawa,H.: "Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer." Genes,Chromosomes & Cancer. 23. 74-77 (1998)

[Publications] Ouyang,H.: "The BAX gene,the promoter of apoptosis,mutated in genetically unstable cancers of the colorectum,stomach,and genetically unstable cancers of the colorectum,stomach,and endometrium." Clinical Cancer Research. 4. 1071-1074 (1998)

[Publications] Kimura,M.: "Identification of two common regions of allelic loss in chromosome arm 12q in human panecrcatic cancer." Cancer Research. 4. 2456-2460 (1998)

[Publications] Matsuzaki,M.: "Detailed deletion mapping on chromosome 1p32-p56 in human colorectal cancer:Identification of three distinct regions of common allelic loss." International Journal of Oncology. 13. 1229-1233 (1998)

[Publications] Sato,M.: "The H-cadherin(CDH13)gene is inactivated in human lung cancer." Human Genetics. 103. 96-101 (1998)

[Publications] Sato,M.: "Chromosome bands 3p14.2,9p21,and 13q14 are mequently deleted in roentgenographically occult bronchogenic squamous cell carcinoma of the lung." Genes,Chromosomes & Cancer. 23. 367-370 (1998)

[Publications] Furukawa,T.: "Genomic analysis of DUSP6,a dual specificity MAP kinase phosphatase,in pancreatic cancer." Cytogenetics and Cell Genetics. 82. 156-159 (1998)

[Publications] Orikasa,K.: "Infrequent genetic altertions of the PTEN gene in Japanese patients with sporadic prostate cancer." Journal of Human Genetics. 43. 228-230 (1998)

[Publications] Fukushige,S.: "Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis." Cancer Research. 58. 4222-4226 (1998)

[Publications] Sato,M.: "A GT dinucleotide repeat polymorpnism in intron 1 of the Hcadherin(CDH13)gene." Journal of Human Genetics. 43. 285-286 (1998)

[Publications] Yoshinaga,K.: "The PTEN,BAX,and IGFIIR genes are mutated in endometria atypical hyperplasia." Japanese Journal of Cancer Research. 89. 985-990 (1998)

[Publications] Yatsuoka,T.: "Genomic analysis of the thymine DNA glycosylase(TDG)gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma." International Journal of Pancreatology. (in press).

[Publications] Mori,Y.: "Chromosome band 16q24 is frequently deleted in human gastric cancer." British Journal of Cancer. (in press).

[Publications] Abe,T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer." Genes,Chromosomes & Cancer. (in press).

[Publications] Han,S.,: "Infrequent somatic mutations of the p73 gene in various human cancers." European Journal of Surgical Oncology. (in press).

[Publications] Kondo,E.: "The human PMS2L proteins do not interact with hMLH,a major DNA mismatch repair protein." Journal of Biochemistry. (in press).

堀井明東北大学, 医学部, 教授 (40249983)