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Previous studies on the survivors of A-bombing and Chernobyl accident have indicated that there is an age difference in incidence and causal gene involved in both leukemia and thyroid cancer. The data on underlying mechanism of age dependency, however, is still limited. In this study, mouse T-cell lymphoma (TL) model was used for investigating the different effect of ionizing radiation to infant age and young adult age-at-exposure. We aimed to clarify the age dependent change of the affected molecular pathways of radiation-induced mouse T-cell lymphomagenesis.\nMaterials and Methods: We analyzed the three groups of TLs developed after irradiation to female B6C3F1 mice weekly to 1.2 Gy X-ray for 4 consecutive weeks starting at infant (1 week of age), prepubertal (4 weeks of age) and adult (8 weeks of age). Loss of heterozygosity (LOH) analyses on chromosome 11, 12 and 19 were performed by PCR using genomic DNA of TLs. Mutations of the Ikaros and Pten were analyzed by sequencing of cDNA and genomic DNA, Western blotting, and array CGH.\nResults and Discussion: The frequency of LOH on chromosome 11 in 1W-TLs (27%; 4/15) was lower than those in 4W (46%; 6/13) and 8W-TLs (63%; 5/8). In contrast, the frequency of LOH on chromosome 19 in 1W-TLs (60%; 9/15) was higher than those in 4W-TLs (31%; 4/13) and 8W-TLs (13%; 1/8). Thus, LOH frequency was altered dependent on the age-at-exposure. Array CGH analysis revealed that intragenic deletion within Ikaros locus, which is mapped on chromosome 11, was characteristic in 1W-TLs, which produced aberrant Ikaros isoform, a lack of exon 5. On the other hand, different size deletions were found in each allele in 8W-TLs; one is intragenic deletion and the other is wide deletion including whole Ikaros locus. This type deletion caused null expression of Ikaros. In 4W-TLs, either type of deletion was found. Thus, deletion type in Ikaros region was different depend on the age-at-exposure. Array-CGH analysis revealed that the genomic copy number of the defined region of chromosome 19 in 1W-TLs was unchanged despite LOH, suggesting the LOH was caused by mitotic recombination. Therefore, it is considered that one allele deletion or intragenic mutation was formed at first and then the mitotic recombination occurred, resulting in homozygous deletion or homozygous intragenic mutations in 1W-TLs. Mutation frequency of Pten was higher than that in 4W- and 8W-TLs.\nConclusion: Ikaros mutation was more involved in older age-at-exposure for T-cell lymphomagenesis, while Pten mutation was more involved in younger age-at-exposure. 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  1. 学会発表・講演等
  2. ポスター発表

Age dependency of Ikaros and Pten alterations in radiation-induced T-cell lymphoma

https://repo.qst.go.jp/records/70786
https://repo.qst.go.jp/records/70786
dec40751-6d22-4cc4-b5e1-2f1ddc5a6dae
Item type 会議発表用資料 / Presentation(1)
公開日 2012-06-05
タイトル
タイトル Age dependency of Ikaros and Pten alterations in radiation-induced T-cell lymphoma
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_c94f
資源タイプ conference object
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Sunaoshi, Masaaki

× Sunaoshi, Masaaki

WEKO 695428

Sunaoshi, Masaaki

Search repository
Amasaki, Yoshiko

× Amasaki, Yoshiko

WEKO 695429

Amasaki, Yoshiko

Search repository
Hirano, Shinobu

× Hirano, Shinobu

WEKO 695430

Hirano, Shinobu

Search repository
Takabatake, Takashi

× Takabatake, Takashi

WEKO 695431

Takabatake, Takashi

Search repository
Morioka, Takamitsu

× Morioka, Takamitsu

WEKO 695432

Morioka, Takamitsu

Search repository
Nishimura, Mayumi

× Nishimura, Mayumi

WEKO 695433

Nishimura, Mayumi

Search repository
Shimada, Yoshiya

× Shimada, Yoshiya

WEKO 695434

Shimada, Yoshiya

Search repository
Tachibana, Akira

× Tachibana, Akira

WEKO 695435

Tachibana, Akira

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Kakinuma, Shizuko

× Kakinuma, Shizuko

WEKO 695436

Kakinuma, Shizuko

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砂押 正章

× 砂押 正章

WEKO 695437

en 砂押 正章

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甘崎 佳子

× 甘崎 佳子

WEKO 695438

en 甘崎 佳子

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坂入 しのぶ

× 坂入 しのぶ

WEKO 695439

en 坂入 しのぶ

Search repository
高畠 貴志

× 高畠 貴志

WEKO 695440

en 高畠 貴志

Search repository
森岡 孝満

× 森岡 孝満

WEKO 695441

en 森岡 孝満

Search repository
西村 まゆみ

× 西村 まゆみ

WEKO 695442

en 西村 まゆみ

Search repository
島田 義也

× 島田 義也

WEKO 695443

en 島田 義也

Search repository
立花 章

× 立花 章

WEKO 695444

en 立花 章

Search repository
柿沼 志津子

× 柿沼 志津子

WEKO 695445

en 柿沼 志津子

Search repository
抄録
内容記述タイプ Abstract
内容記述 Background: Radiation carcinogenesis is greatly dependent on the age-at-exposure. Previous studies on the survivors of A-bombing and Chernobyl accident have indicated that there is an age difference in incidence and causal gene involved in both leukemia and thyroid cancer. The data on underlying mechanism of age dependency, however, is still limited. In this study, mouse T-cell lymphoma (TL) model was used for investigating the different effect of ionizing radiation to infant age and young adult age-at-exposure. We aimed to clarify the age dependent change of the affected molecular pathways of radiation-induced mouse T-cell lymphomagenesis.
Materials and Methods: We analyzed the three groups of TLs developed after irradiation to female B6C3F1 mice weekly to 1.2 Gy X-ray for 4 consecutive weeks starting at infant (1 week of age), prepubertal (4 weeks of age) and adult (8 weeks of age). Loss of heterozygosity (LOH) analyses on chromosome 11, 12 and 19 were performed by PCR using genomic DNA of TLs. Mutations of the Ikaros and Pten were analyzed by sequencing of cDNA and genomic DNA, Western blotting, and array CGH.
Results and Discussion: The frequency of LOH on chromosome 11 in 1W-TLs (27%; 4/15) was lower than those in 4W (46%; 6/13) and 8W-TLs (63%; 5/8). In contrast, the frequency of LOH on chromosome 19 in 1W-TLs (60%; 9/15) was higher than those in 4W-TLs (31%; 4/13) and 8W-TLs (13%; 1/8). Thus, LOH frequency was altered dependent on the age-at-exposure. Array CGH analysis revealed that intragenic deletion within Ikaros locus, which is mapped on chromosome 11, was characteristic in 1W-TLs, which produced aberrant Ikaros isoform, a lack of exon 5. On the other hand, different size deletions were found in each allele in 8W-TLs; one is intragenic deletion and the other is wide deletion including whole Ikaros locus. This type deletion caused null expression of Ikaros. In 4W-TLs, either type of deletion was found. Thus, deletion type in Ikaros region was different depend on the age-at-exposure. Array-CGH analysis revealed that the genomic copy number of the defined region of chromosome 19 in 1W-TLs was unchanged despite LOH, suggesting the LOH was caused by mitotic recombination. Therefore, it is considered that one allele deletion or intragenic mutation was formed at first and then the mitotic recombination occurred, resulting in homozygous deletion or homozygous intragenic mutations in 1W-TLs. Mutation frequency of Pten was higher than that in 4W- and 8W-TLs.
Conclusion: Ikaros mutation was more involved in older age-at-exposure for T-cell lymphomagenesis, while Pten mutation was more involved in younger age-at-exposure. These results suggest that a target gene of radiation-induced T-cell lymphomagenesis and molecular mechanism of mutation change as a function of age-at-exposure.
会議概要(会議名, 開催地, 会期, 主催者等)
内容記述タイプ Other
内容記述 Childhood Cancer 2012 -International scientific conference on early exposure and childhood cancer-
発表年月日
日付 2012-04-26
日付タイプ Issued
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