Mutation status of epidermal growth factor receptor family gene in head and neck squamous cell carcinoma and its drug-sensitivity to small molecule inhibitors.

头颈鳞癌表皮生长因子受体家族基因突变状况及其对小分子抑制剂的敏感性。

• 批准号: 21592207
• 负责人: YUZA Yuki
• 金额: $ 2.91万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592207/
• 关键词: 頭頸部扁平上皮がん; 表皮成長因子受容体; 遺伝子変異; 分子標的薬; ゲノム医科学

We explored mutation status of epidermal growth factor receptor, EGFR, family gene using 92 head and neck squamous cell carcinoma, HNSCC, samples. 5 mutations of EGFR, L858R, E709K, V765G, G1022S, and ins770G, in 6 samples and 1 mutation of HER2, K716E, in 1 sample have been recognized. Of these mutations, L858R, E709K and ins770G could render the growth of Ba/F3 cells independent of IL-3 by the constitutive autophosphorylation of EGFR. L858R and E709K showed sensitivity to EGFR inhibitors, although ins770G showed relatively resistance to those inhibitors.Only one out of 31 lymph node metastases showed the same EGFR mutation of the primary site, L858R.Also we examined mutation status of down-stream genes of EGFR pathway, K-Ras, B-Raf and PIK3CA. And we found 3 each already known mutations of K-Ras and PIK3CA.

我们采用92例头颈部鳞状细胞癌（HNSCC）标本检测表皮生长因子受体（EGFR）家族基因突变情况。在6个样本中识别出5个EGFR突变，即L 858 R、E709 K、V765 G、G1022 S和ins 770 G，在1个样本中识别出1个HER 2突变，即K716 E。其中L 858 R、E709 K和ins 770 G突变可使Ba/F3细胞的生长不依赖于IL-3，这是由于EGFR的组成性自身磷酸化。L 858 R和E709 K对EGFR抑制剂敏感，而ins 770 G对EGFR抑制剂相对耐药; 31例淋巴结转移瘤中仅有1例发生相同的EGFR原发位点突变，即L 858 R;同时检测EGFR通路下游基因K-Ras、B-Raf和PIK 3CA的突变情况。我们发现K-Ras和PIK 3CA各有3个已知突变。

项目成果

頭頸部癌におけるEGFRファミリー(HER1～HER4)の遺伝子解析と薬剤感受性の検討

EGFR家族（HER1至HER4）的遗传分析及头颈癌药物敏感性研究

• 发表时间: 2010
• 作者: 濱孝憲;須田稔士;清野洋一;加藤孝邦;森山寛
• 通讯作者: 森山寛

Mutation analysis of PIK3CA, KRAS, BRAF and corresponding EGFR status in head and neck squamous cell carcinoma

头颈鳞癌PIK3CA、KRAS、BRAF及相应EGFR状态突变分析

• 发表时间: 2011
• 作者: Toshihito Suda;Takanori Hama;Susumu Okano;Youichi Seino;Yuki Yuza;Takakuni Kato;Hiroshi Moriyama
• 通讯作者: Hiroshi Moriyama

Prognostic Significance of Vitamin D Receptor Polymorphisms in Head and Neck Squamous Cell Carcinoma

• DOI: 10.1371/journal.pone.0029634
• 发表时间: 2011-12-29
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Hama, Takanori;Norizoe, Chihiro;Urashima, Mitsuyoshi
• 通讯作者: Urashima, Mitsuyoshi

Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma

• DOI: 10.1634/theoncologist.2009-0058
• 发表时间: 2009-01-01
• 期刊: ONCOLOGIST
• 影响因子: 5.8
• 作者: Hama, Takanori;Yuza, Yuki;Urashima, Mitsuyoshi
• 通讯作者: Urashima, Mitsuyoshi

頭頸部癌における上皮成長因子受容体(EGFR)遺伝子変異とリン酸化の検討(再発予後因子の検討)

头颈癌表皮生长因子受体（EGFR）基因突变和磷酸化检查（复发预后因素检查）

• 发表时间: 2009
• 作者: 濱孝憲;須田稔士;清野洋一;浦島充佳;加藤孝邦
• 通讯作者: 加藤孝邦