Misc - SUZUKI Hiromu

Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype

M Toyota, N Ahuja, H Suzuki, F Itoh, M Ohe-Toyota, K Imai, SB Baylin, JPJ Issa

CANCER RESEARCH ( AMER ASSOC CANCER RESEARCH )  59 ( 21 ) 5438 - 5442  1999.11

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Aberrant methylation of 5' CpG islands is thought to play an important role in the inactivation of tumor suppressor genes in cancer. In colorectal cancer, a group of tumors is characterized by a hypermethylator phenotype termed CpG island methylator phenotype (CIMP), which includes methylation of such genes as p16 and hMLH1, To study whether CIMP is present in gastric cancer, the methylation status of five newly cloned CpG islands was examined in 56 gastric cancers using bisulfite-PCR, Simultaneous methylation of three loci or more was observed in 23 (41%) of 56 cancers, which suggests that these tumors have the hypermethylator phenotype CIMP, There was a significant concordance between CIMP and the methylation of known genes including p16, and hMLH1; methylation of p16 was detected in 16 (70%) of 23 CIMP+ tumors, 1 (8%) of 12 CIMP intermediate tumors, and 1 (5%) of 21 CIMP- tumors (P < 0.0001). Methylation of the hMLH1 gene was defected in three of five tumors that showed microsatellite instability, and all three of the cases were CIMP+. The CIMP phenotype is an early event in gastric cancer, being present in the normal tissue adjacent to cancer in 5 of 56 cases. These results suggest that CIMP may be one of the major pathways that contribute to tumorigenesis in gastric cancers.

Distinct methylation pattern and microsatellite instability in sporadic gastric cancer

H Suzuki, F Itoh, M Toyota, T Kikuchi, H Kakiuchi, Y Hinoda, K Imai

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS )  83 ( 3 ) 309 - 313  1999.10

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Aberrant 5' CpG island methylation is an alternative mechanism of gene inactivation during the development of cancer as demonstrated for several tumor-suppressor genes. Also, marked relationship of microsatellite instability (MSI) and DNA methylation has been reported in sporadic colorectal cancer, which is a result of epigenetic inactivation of hMLHI in association of promoter hypermethylation, In the present study, we investigated the 5' CpG island hypermethylation of hMLHI, E-cadherin and p16 in 61 primary gastric cancers (GCs) by using combined bisulfite restriction analysis (COBRA) and methylation-specific FCR (MSP), and their MSI status. Of 61 GCs investigated, 5 (8.1%) tumors presented hMLHI methylation, 16 (26.2%) and 25 (40.9%) showed E-cadherin and p16 methylation respectively, and 8 (13.1%) presented high-frequency MSI (MSI-H). Of the a MSI-H patients, 5 presented hMLHI methylation, whereas no low-frequency MSI (MSI-L) and microsatellite stable (MSS) cases exhibited hMLHI methylation (5/8 vs. 0/43, p<0.00001). Furthermore, these patients also presented E-cadherin and p16 hypermethylation. Our data showed a significant correlation between hMLHI methylation and MSI in GC, and suggested that a common mechanism of aberrant de novo methylation can be postulated in these cancers. (C) 1999 Wiley-Liss, Inc.

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G2/M期集積細胞において発現が亢進している遺伝子の単離と解析 : differential display 法を用いて

佐々木 泰史, 伊東 文生, 垣内 英樹, 鈴木 拓, 吉田 幸成, 日野田 裕治, 今井 浩三, 谷内 昭

生物物理化学 = Journal of Electrophoresis   42   29 - 29  1998.09

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胃癌におけるp16/CDKN2遺伝子プロモーター領域のメチル化

鈴木 拓, 伊東 文生, 豊田 実, 菊池 剛史, 垣内 英樹, 日野田 裕治, 今井 浩三

生物物理化学 = Journal of Electrophoresis   42   25 - 25  1998.09

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[Hereditary macrothrombocytopenia]

Kaoru KASAHARA, Tohru TAKAHASHI, Fumie HAMAMOTO, Toshiaki HAYASHI, Masaaki ADACHI, Hirosuke OKUDA, Shuji SATOH, Yuji HINODA, Kohzoh IMAI

Rinsho Ketsueki ( The Japanese Society of Hematology )  39 ( 4 ) 308 - 313  1998

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A 19 year-old male was referred to our department because of macrothrombocytopenia. His platelet count was 73,000/μl and giant platelets were observed in the peripheral blood smear specimen. Though he had been suffering from severe atopic dermatitis for four years, he seemed to be healthy without bleeding tendency. When he underwent a shunt operation for tetralogy of Fallot without any complication at nine-years old, thrombocytopenia was allegedly pointed out for the first time. Bone marrow aspiration revealed no abnormal findings with no chromosomal aberration. Normal platelet aggregation responses against adenosine diphosphate, epinephrine, collagen, and ristocetin were observed. The platelet adhesiveness (modified Salzman method) was slightly elevated. Unlike other reported syndromes associated with macrothrombocytopenia, his leukocytes had no inclusion bodies. His mother also had macrothrombocytopenia thus, this disorder was suspected to be hereditary.

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A case of anaplastic carcinoma of the pancreas with high serum IL-6 level

SUZUKI Hiromu, ENDO Takao, YAWATA Atsushi, AZUMA Naoki, ITO Fumio, IMAI Kohzoh

膵臓 = The Journal of Japan Pancreas Society   12 ( 1 ) 59 - 64  1997.02

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[Rapidly progressed chronic myelomonocytic leukemia associated with severe skin infiltration]

Hiromu SUZUKI, Tohru TAKAHASHI, Toshiaki HAYASHI, Hajime KANAMOTO, Fumie HAMAMOTO, Masaaki ADACHI, Yuji HINODA, Kohzoh IMAI

Rinsho Ketsueki ( The Japanese Society of Hematology )  38 ( 9 ) 752 - 756  1997

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A 79-year-old man developed nodular skin eruption in his trunk in March 1995. He was diagnosed as CTCL and hospitalized to the department of dermatology and low dose VP-16 therapy was started. 6 months later, he was referred to our department because of severe melena. On admission, marked monocytosis was observed both in the bone marrow (43.6%) and peripheral blood (monocyte>1,000/μl). Skin biopsy showed infiltration of large mononuclear cells in the dermis and subcutaneous tissue. Thus a diagnosis of CMML with skin infiltration was made. Skin eruption developed over his entire skin and peripheral monocytes increased over 5,000/μl. Chemotherapy was started and skin infiltration was slightly improved, but the disease developed into acute phase and he died 3 months after admission.

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