BACKGROUND Gastrointestinal stromal tumors(GISTs)are generally characterized by driver mutations in KIT or PDGFRA.However,the molecular landscape of wild-type GISTs remains complex,posing significant therapeutic chall...BACKGROUND Gastrointestinal stromal tumors(GISTs)are generally characterized by driver mutations in KIT or PDGFRA.However,the molecular landscape of wild-type GISTs remains complex,posing significant therapeutic challenges.Recent evidence has indicated alterations in FGFR2 as potential oncogenic drivers in patients with various cancers.However,the role of these drivers in GIST pathogenesis remains underexplored.CASE SUMMARY We retrospectively evaluated two patients with GIST,diagnosed between August 2021 and July 2022,harboring FGFR2 mutations through hybrid capture-based next-generation sequencing(NGS).We analyzed their clinicopathological characteristics,treatment response,and long-term follow-up data.Both patients,a 47-year-old man(case 1)and a 43-year-old woman(case 2),underwent successful surgical resection and received adjuvant imatinib therapy.They achieved sustained remission with a median follow-up of 28 months.Notably,the NGS revealed novel FGFR2 rearrangements,an FGFR2-CIT/intergenic-FGFR2 fusion in case 1 and FGFR2-CAMK2G/FGFR2-VCL fusions in case 2 without canonical KIT or PDGFRA mutations.Both patients exhibited a favorable response to standard imatinib treatment.CONCLUSION Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs.These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases,warranting further investigation in larger cohorts.展开更多
目的通过对1例新生儿期特殊面容、神经系统结构畸形患儿进行全外显子组序列检测分析,旨在为该患儿寻找潜在的致病原因。方法纳入1例在复旦大学附属儿科医院(我院)新生儿病房住院期间未能明确诊断的多发畸形患儿,主要临床表型为前额突出...目的通过对1例新生儿期特殊面容、神经系统结构畸形患儿进行全外显子组序列检测分析,旨在为该患儿寻找潜在的致病原因。方法纳入1例在复旦大学附属儿科医院(我院)新生儿病房住院期间未能明确诊断的多发畸形患儿,主要临床表型为前额突出、腭弓高、耳位低、枕部较平,双侧脑室扩大、透明隔部分缺如、胼胝体发育异常,采用Sure Selct Human All Exon捕获试剂盒和Illumina Hi Seq2000测序平台,行全外显子组序列检测。数据分析采用复旦大学附属儿科医院转化中心所建立的高通量测序数据分析流程。采用Sanger测序进行验证。结果患儿全外显子组序列检测数据,共检测到79 064个变异,经过质量控制筛选、变异频率筛选、变异分类筛选,剩余645个变异。在进一步分析中,645个变异中有159个其所在基因在OMIM数据库及HGMD数据库与疾病相关。从3个已经报道的突变位点中锁定致病突变为FGFR2基因(NM_000141)c.C1040G,p.S347C。Sanger测序在家系内验证该位点为新发(de novo)突变。结论采用全外显子组序列检测,明确诊断FGFR2相关疾病1例。并且结合我院已经建立的高通量测序数据分析和临床诊断流程,为新生儿多发畸形寻找潜在的致病基因提供了快速、高效的方法。展开更多
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are generally characterized by driver mutations in KIT or PDGFRA.However,the molecular landscape of wild-type GISTs remains complex,posing significant therapeutic challenges.Recent evidence has indicated alterations in FGFR2 as potential oncogenic drivers in patients with various cancers.However,the role of these drivers in GIST pathogenesis remains underexplored.CASE SUMMARY We retrospectively evaluated two patients with GIST,diagnosed between August 2021 and July 2022,harboring FGFR2 mutations through hybrid capture-based next-generation sequencing(NGS).We analyzed their clinicopathological characteristics,treatment response,and long-term follow-up data.Both patients,a 47-year-old man(case 1)and a 43-year-old woman(case 2),underwent successful surgical resection and received adjuvant imatinib therapy.They achieved sustained remission with a median follow-up of 28 months.Notably,the NGS revealed novel FGFR2 rearrangements,an FGFR2-CIT/intergenic-FGFR2 fusion in case 1 and FGFR2-CAMK2G/FGFR2-VCL fusions in case 2 without canonical KIT or PDGFRA mutations.Both patients exhibited a favorable response to standard imatinib treatment.CONCLUSION Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs.These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases,warranting further investigation in larger cohorts.
文摘目的通过对1例新生儿期特殊面容、神经系统结构畸形患儿进行全外显子组序列检测分析,旨在为该患儿寻找潜在的致病原因。方法纳入1例在复旦大学附属儿科医院(我院)新生儿病房住院期间未能明确诊断的多发畸形患儿,主要临床表型为前额突出、腭弓高、耳位低、枕部较平,双侧脑室扩大、透明隔部分缺如、胼胝体发育异常,采用Sure Selct Human All Exon捕获试剂盒和Illumina Hi Seq2000测序平台,行全外显子组序列检测。数据分析采用复旦大学附属儿科医院转化中心所建立的高通量测序数据分析流程。采用Sanger测序进行验证。结果患儿全外显子组序列检测数据,共检测到79 064个变异,经过质量控制筛选、变异频率筛选、变异分类筛选,剩余645个变异。在进一步分析中,645个变异中有159个其所在基因在OMIM数据库及HGMD数据库与疾病相关。从3个已经报道的突变位点中锁定致病突变为FGFR2基因(NM_000141)c.C1040G,p.S347C。Sanger测序在家系内验证该位点为新发(de novo)突变。结论采用全外显子组序列检测,明确诊断FGFR2相关疾病1例。并且结合我院已经建立的高通量测序数据分析和临床诊断流程,为新生儿多发畸形寻找潜在的致病基因提供了快速、高效的方法。
