Dataset Information

Novel somatic Missense Mutations in Exon 11 of the KIT Gene are Detected in Melanoma.

ABSTRACT:

Objective

The aim of the present study was to analyze mutations of the mast/stem cell growth factor receptor Kit (KIT) gene in patients with melanoma from Eastern Siberia regions of the Russian Federation.

Methods

KIT gene mutations in exons 11 and 13 were analyzed by Sanger sequencing in 57 tumor samples obtained from patients with KIT-positive melanomas localized in preferable locations.

Result

Mutations were identified in 21% of patients. Among them, multiple mutations were identified in five patients. A total of 18 mutations were observed in the KIT gene, of which three were deletions and fourteen substitution mutations. Age, gender and clinicopathological characteristics of patients with cutaneous KIT-positive melanoma in Eastern Siberia corresponded to the European population. According to computational prediction tools, all mutations were evaluated as potentially harmful.

Conclusion

The six novel mutations reported in the present study expand our knowledge on the molecular pathogenesis of melanoma, which can be used to further explore methods to improve disease therapeutic strategies.

SUBMITTER: Palkina N

PROVIDER: S-EPMC10762753 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Novel somatic Missense Mutations in Exon 11 of the KIT Gene are Detected in Melanoma.

Palkina Nadezhda N Tyumentseva Anna A Ruksha Tatiana T

Asian Pacific journal of cancer prevention : APJCP 20230901 9

<h4>Objective</h4>The aim of the present study was to analyze mutations of the mast/stem cell growth factor receptor Kit (KIT) gene in patients with melanoma from Eastern Siberia regions of the Russian Federation.<h4>Methods</h4>KIT gene mutations in exons 11 and 13 were analyzed by Sanger sequencing in 57 tumor samples obtained from patients with KIT-positive melanomas localized in preferable locations.<h4>Result</h4>Mutations were identified in 21% of patients. Among them, multiple mutations w ...[more]

PMID: 37774052

Similar Datasets

Project description:Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of c-KIT in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), all of which have been implicated in human GISTs.Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples.Of these seventeen cases, six amplicons of exon 11 of c-KIT showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of c-KIT and exons 12 and 14 of PDGFRA.The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of c-KIT in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other c-KIT or PDGFRA exons showed any abnormalities in our cases. This finding underlines the critical importance of c-KIT in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in c-KIT implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in c-KIT may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further demonstrates that spontaneously occurring canine GISTs share molecular features with human GISTs and are an appropriate model for human GISTs.

Project description:BackgroundMutation screening for gastrointestinal stromal tumor (GIST) is crucial and the c kit gene (KIT) exon 11 mutation is the most common type. This study aimed to explore the associations between GIST with KIT exon 11 mutation and contrast-enhanced computed tomography (CT) images.MethodsPathologically proven GISTs with definitive genotype testing results in our hospital were retrospectively included. Abdominal contrast-enhanced CT images were analyzed. Conventional CT image features and radiomic features were recorded and extracted to build the following models: model [CT], model [radiomic + clinic] and model [CT + radiomic + clinic]. The diagnostic performances of GISTs with KIT exon 11 mutation and KIT exon 11 deletion involving codons 557-558 were evaluated.ResultsIn total, 327 GISTs (255 with KIT exon 11 mutation, and 73 with KIT exon 11 mutation deletion involving codons 557-558) were included. Significant CT features were found for GISTs with KIT exon 11 mutation. The area under curves (AUCs) of the models for KIT exon 11 mutation were 0.7158, 0.7530, and 0.8375 in the training cohort, and 0.6777, 0.7349, and 0.8105 in validation cohort, respectively. The AUCs of the models for KIT exon 11 mutation deletion involving codons 557-558 were 0.7155, 8621, and 0.8691 in the training cohort, and 0.7099, 0.8355, and 0.8488 in the validation cohort, respectively. The model [CT + radiomic + clinic] demonstrated the highest AUCs for prediction of KIT exon 11 mutation and those with deletion involving codons 557-558 (P<0.05), respectively. The model [radiomic + clinic] showed higher diagnostic performance than model [CT] significantly.ConclusionsOur results demonstrated the associations between GIST with KIT exon 11 mutation and contrast-enhanced CT images. We found combing conventional image analysis and texture analysis is a useful tool to distinguish GIST with KIT exon 11 mutation. CT radiogenomics exhibited good application potential in predict the KIT exon 11 mutation of GIST.

Dataset Information

Novel somatic Missense Mutations in Exon 11 of the KIT Gene are Detected in Melanoma.

Objective

Methods

Result

Conclusion

Publications

Novel somatic Missense Mutations in Exon 11 of the KIT Gene are Detected in Melanoma.

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