PDGFRA mutation

These cases underscore the importance of interpreting SDHA variants carefully, as the identification of germline SDHA variants does not always indicate the need for aggressive surveillance or intervention. Germline SDHA variants increase the risk of PPGLs and wild-type GISTs.The penetrance of germline SDHA variants in carriers without an SDHA-related tumour is low.Careful clinical assessment is essential to determine if a patient with an SDHA germline mutation has an SDHA-related tumour.This is particularly complex in GISTs, as only wild-type GISTs (those without somatic variants in c-Kit or PDGFRA) are likely to be SDHA-related.Immunohistochemistry for expression of SDH subunits can help clarify whether a tumour is related to SDHA variants.

The remaining patient had an unresectable tumor and received tyrosine kinase inhibitor therapy; however, sequential treatment with imatinib and sunitinib was clinically ineffective. However, their clinical behavior differs: D842Y-mutant GISTs consistently present as large, hypervascular tumors associated with acute complications. The therapeutic efficacy of tyrosine kinase inhibitors remains unclear, underscoring the need for further case accumulation to better define the clinical course and determine optimal treatment strategies for this rare subtype.

While endoscopic resection is preferred for localized lesions, surgical intervention remains necessary in complex or obstructive cases. Understanding IFPs' molecular profile and cellular origin may refine future diagnostic and therapeutic approaches.

In vitro modeling demonstrated that EML4::NTRK3 confers imatinib resistance, while sensitizing GIST cells to NTRK inhibitors. This first reported instance of an NTRK fusion as a secondary event in GIST progression underscores the importance of testing for NTRK alterations in tumors that have developed resistance to tyrosine kinase inhibitors to ensure patients are offered all available therapeutic options.

P1/2, N=29, Completed, Blueprint Medicines Corporation | Active, not recruiting --> Completed

While imatinib revolutionized first-line therapy, resistance and specific mutation profiles necessitate subsequent generations of tyrosine kinase inhibitors (TKIs). Second- and third-generation TKIs have transformed the management of advanced GIST, extending survival and offering mutation-specific precision therapy. Ongoing research into resistance mechanisms, combination strategies, and novel inhibitors promises further optimization of patient-centered care.

Western blot and qRT-PCR tests validated these genes in GIST-T1 cells, and ssGSEA analysis indicated a significant relationship between these hub genes and immune cell infiltration. This study revealed a set of novel signature genes with high diagnostic value, offering promising targets for the diagnosis and treatment of GIST.

First-generation sequencing identified concurrent mutations in c-KIT exons 11 (V560D) and exon 17 (N822K), implicating these double mutations in acquired imatinib resistance. This case underscores the clinical significance of double mutations in GIST, the limitations of first-line therapy in such contexts, and the importance of early genetic profiling to inform personalized treatment strategies.

Their disease progression and prognosis are generally more favorable compared to adult-type high-grade gliomas. Molecular testing plays a crucial role in diagnosis and differential diagnosis, holding significant importance for treatment and prognosis evaluation.

Interestingly, the tumors exhibited different morphologies (epithelioid and spindle cell), distinct immunohistochemical profiles, and harbored different mutations (KIT and PDGFRA).ConclusionSporadic multiple gastrointestinal stromal tumors may have different morphological and immunohistochemical features, and they may also harbor two mutually exclusive mutations, such as KIT and PDGFRA. Recognition of this possibility is crucial for accurate diagnosis and the development of personalized therapy.

Mutations were 12 to 39 nucleotide deletion or duplication variants. Our results suggest that short read, amplicon-based NGS assays may miss a significant number of clinically actionable KIT mutations and that follow-up of KIT and PDGFRA NGS-negative cases by alternative testing modalities should be considered.

Our findings highlight the clinical relevance of integrating NGS into routine GIST management, particularly for the identification and interpretation of rare genetic variants. The study underscores the importance of data sharing and collective variant annotation to support accurate molecular classification, prognostic assessment, and therapeutic decision-making for individual patients.