Department of Clinical Oncology, Akita University, Akita, Japan.
Department of Pediatrics, Akita University, Akita, Japan.
Jpn J Clin Oncol. 2020 Sep 28;50(10):1214-1217. doi: 10.1093/jjco/hyaa095.
Germline mutations of TP53 are responsible for Li-Fraumeni syndrome in its 60-80%. We found a novel germline mutation, TP53: c.997del:p.R333Vfs12 (NM_000546.6, GRCh, 17:7670713..7670713). The proband is a 40-year-old female, who was suffered from osteosarcoma in her right forearm at her age of 11. She was also suffered from lung adenocarcinoma in her right upper lobe and bone metastasis in her right scapula at her age of 37. She was treated with gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) because of EGFR mutation (L747-S752 del). Her bone metastasis became resistant after 1-year treatment. Bone metastasis had an additional EGFR mutation (T790M). The secondary treatment with osimertinib, an another EGFR-TKI, can successfully control the tumors for over 2 years. This TP53 mutation (R333Vfs12) was first found in lung adenocarcinomas. The therapeutic effect of osimertinib for this triple mutant lung adenocarcinoma is better than the previous report.
胚系 TP53 突变负责 Li-Fraumeni 综合征的 60-80%。我们发现了一种新的胚系突变，TP53:c.997del:p.R333Vfs12（NM_000546.6，GRCh，17:7670713..7670713）。先证者是一名 40 岁女性，11 岁时右前臂患有骨肉瘤，37 岁时右肺上叶患有肺腺癌和右肩胛骨骨转移。由于存在 EGFR 突变（L747-S752del），她接受了表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）吉非替尼治疗。治疗 1 年后，她的骨转移出现耐药。骨转移还有另外一个 EGFR 突变（T790M）。二线治疗使用奥希替尼，另一种 EGFR-TKI，可以成功控制肿瘤超过 2 年。这种 TP53 突变（R333Vfs12）首先在肺腺癌中发现。奥希替尼治疗这种三突变肺腺癌的疗效优于之前的报道。
