A 51-year-old,male,non-smoker with a 3.4 cm mass in the right middle lobe was diagnosed with large cell neuroendocrine carcinoma(LCNEC).Fluorescence in situ hybridization revealed anaplastic lymphoma kinase(ALK)gene t...A 51-year-old,male,non-smoker with a 3.4 cm mass in the right middle lobe was diagnosed with large cell neuroendocrine carcinoma(LCNEC).Fluorescence in situ hybridization revealed anaplastic lymphoma kinase(ALK)gene translocation,in agreement with the immunohistochemistry result obtained with use of ALK-Ventana.Radiographic examinations showed both bone and brain metastasis.After two cycles of chemotherapy consisting of etoposide and cisplatin,the patient achieved stable disease,and was subsequently switched to crizotinib.Both computed tomography and magnetic resonance imaging revealed partial response after 4 months of crizotinib,but progressed after treatment for 10 months,when several hard lymph nodes were palpable in the left supraclavicular fossa.Lymph node biopsy showed similar histology of tumor cells and targeted next-generation sequencing revealed ALK F1174L on exon 23 with two rare forms of ALK rearrangements.This case provides evidence of responsiveness of ALK inhibitors for a rare pattern of ALK-rearranged LCNEC,and suggests that F1174L,a common resistant mutation found in non-small-cell lung cancer,also causes crizotinib resistance in LCNEC.展开更多
Li-Fraumeni syndrome(LFS),a rare autosomal-dominant inheritance condition,is associated with a family cancer history as well as pathogenic/likely-pathogenic TP53 germline variants(P/LP TP53 GV).The current clinical me...Li-Fraumeni syndrome(LFS),a rare autosomal-dominant inheritance condition,is associated with a family cancer history as well as pathogenic/likely-pathogenic TP53 germline variants(P/LP TP53 GV).The current clinical methods for detecting LFS are limited.Here,we retrospectively investigate P/LP TP53 GV among Chinese cancer patients by next-generation sequencing and evaluate its relationship with a family cancer history.A total of 270 out of 19,226 cancer patients have TP53 GV,including 53 patients with P/LP TP53 GV.Patients with P/LP TP53 GV are mainly found in male with glioma,lung cancer or sarcoma.The median age of diagnosis for P/LP TP53 GV patients is significantly lower than that of non-P/LP TP53 GV patients(31-years vs.53-years;P<0.01).One LFS patient and 3 Li-Fraumeni-like syndrome(LFL)patients are among the 26 followed-up P/LP TP53 GV patients.Among 25 types of P/LP TP53 GV,the highest variant frequencies occurred at codon 175 and 248.p.M237 I,p.R158 H,p.C238 Y and p.C275 R,are firstly identified among the Chinese LFS/LFL patients.This study reports the(P/LP)TP53 GV characteristics of Chinese pan-cancer patients.These findings suggest analyzing the P/LP TP53 GV in cancer patients is an effective strategy for identifying cancer predisposition syndrome.展开更多
基金supported by the National Key Development Plan for Precision Medicine Research(2017YFC0910004)the Transformation Projects of Sci-Tech Achievements of Sichuan Province(2016CZYD0001)the Sci-Tech Support Program of Science and Technology Department of Sichuan Province(2016SZ0073)。
文摘A 51-year-old,male,non-smoker with a 3.4 cm mass in the right middle lobe was diagnosed with large cell neuroendocrine carcinoma(LCNEC).Fluorescence in situ hybridization revealed anaplastic lymphoma kinase(ALK)gene translocation,in agreement with the immunohistochemistry result obtained with use of ALK-Ventana.Radiographic examinations showed both bone and brain metastasis.After two cycles of chemotherapy consisting of etoposide and cisplatin,the patient achieved stable disease,and was subsequently switched to crizotinib.Both computed tomography and magnetic resonance imaging revealed partial response after 4 months of crizotinib,but progressed after treatment for 10 months,when several hard lymph nodes were palpable in the left supraclavicular fossa.Lymph node biopsy showed similar histology of tumor cells and targeted next-generation sequencing revealed ALK F1174L on exon 23 with two rare forms of ALK rearrangements.This case provides evidence of responsiveness of ALK inhibitors for a rare pattern of ALK-rearranged LCNEC,and suggests that F1174L,a common resistant mutation found in non-small-cell lung cancer,also causes crizotinib resistance in LCNEC.
文摘Li-Fraumeni syndrome(LFS),a rare autosomal-dominant inheritance condition,is associated with a family cancer history as well as pathogenic/likely-pathogenic TP53 germline variants(P/LP TP53 GV).The current clinical methods for detecting LFS are limited.Here,we retrospectively investigate P/LP TP53 GV among Chinese cancer patients by next-generation sequencing and evaluate its relationship with a family cancer history.A total of 270 out of 19,226 cancer patients have TP53 GV,including 53 patients with P/LP TP53 GV.Patients with P/LP TP53 GV are mainly found in male with glioma,lung cancer or sarcoma.The median age of diagnosis for P/LP TP53 GV patients is significantly lower than that of non-P/LP TP53 GV patients(31-years vs.53-years;P<0.01).One LFS patient and 3 Li-Fraumeni-like syndrome(LFL)patients are among the 26 followed-up P/LP TP53 GV patients.Among 25 types of P/LP TP53 GV,the highest variant frequencies occurred at codon 175 and 248.p.M237 I,p.R158 H,p.C238 Y and p.C275 R,are firstly identified among the Chinese LFS/LFL patients.This study reports the(P/LP)TP53 GV characteristics of Chinese pan-cancer patients.These findings suggest analyzing the P/LP TP53 GV in cancer patients is an effective strategy for identifying cancer predisposition syndrome.
