Dataset Information

Introduction and impact of routine whole genome sequencing in the diagnosis and management of sarcoma.

ABSTRACT:

Background

Sarcomas are diverse neoplasms with highly variable histological appearances in which diagnosis is often challenging and management options for metastatic/unresectable disease limited. Many sarcomas have distinctive molecular alterations, but the range of alterations is large, variable in type and rapidly increasing, meaning that testing by limited panels is unable to capture the broad spectrum of clinically pertinent genomic drivers required. Paired whole genome sequencing (WGS) in contrast allows comprehensive assessment of small variants, copy number and structural variants along with mutational signature analysis and germline testing.

Methods

Introduction of WGS as a diagnostic standard for all eligible patients with known or suspected soft tissue sarcoma over a 2-year period at a soft tissue sarcoma treatment centre.

Results

WGS resulted in a refinement in the diagnosis in 37% of cases, identification of a target for personalised therapy in 33% of cases, and a germline alteration in 4% of cases.

Conclusion

Introduction of WGS poses logistical and training challenges, but offers significant benefits to this group of patients.

SUBMITTER: Watkins JA

PROVIDER: S-EPMC11368954 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Publications

Introduction and impact of routine whole genome sequencing in the diagnosis and management of sarcoma.

Watkins James A JA Trotman Jamie J Tadross John A JA Harrington Jennifer J Hatcher Helen H Horan Gail G Prewett Sarah S Wong Han H HH McDonald Sarah S Tarpey Patrick P Roberts Thomas T Su Jing J Tischkowitz Marc M Armstrong Ruth R Amary Fernanda F Sosinsky Alona A

British journal of cancer 20240712 5

<h4>Background</h4>Sarcomas are diverse neoplasms with highly variable histological appearances in which diagnosis is often challenging and management options for metastatic/unresectable disease limited. Many sarcomas have distinctive molecular alterations, but the range of alterations is large, variable in type and rapidly increasing, meaning that testing by limited panels is unable to capture the broad spectrum of clinically pertinent genomic drivers required. Paired whole genome sequencing (W ...[more]

PMID: 38997407

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Project description:Introduction: Monogenic diabetes (MD) accounts for 3%-6% of all cases of diabetes. This prevalence is underestimated due to its overlapping clinical features with type 1 and type 2 diabetes. Hence, genetic testing is the most appropriate tool for obtaining an accurate diagnosis. In Tunisia, few cohorts of MD have been investigated until now. The aim of this study is to search for pathogenic variants among 11 patients suspected of having MD in Tunisia using whole-exome sequencing (WES). Materials and methods: WES was performed in 11 diabetic patients recruited from a collaborating medical center. The pathogenicity of genetic variation was assessed using combined filtering and bioinformatics prediction tools. The online ORVAL tool was used to predict the likelihood of combinations of pathogenic variations. Then, Sanger sequencing was carried out to confirm likely pathogenic predicted variants among patients and to check for familial segregation. Finally, for some variants, we performed structural modeling to study their impact on protein function. Results: We identified novel variants related to MD in Tunisia. Pathogenic variants are located in several MODY and non-MODY genes. We highlighted the presence of syndromic forms of diabetes, including the Bardet-Biedl syndrome, Alström syndrome, and severe insulin resistance, as well as the presence of isolated diabetes with significantly reduced penetrance for Wolfram syndrome-related features. Idiopathic type 1 diabetes was also identified in one patient. Conclusion: In this study, we emphasized the importance of genetic screening for MD in patients with a familial history of diabetes, mainly among admixed and under-represented populations living in low- and middle-income countries. An accurate diagnosis with molecular investigation of MD may improve the therapeutic choice for better management of patients and their families. Additional research and rigorous investigations are required to better understand the physiopathological mechanisms of MD and implement efficient therapies that take into account genomic context and other related factors.

Dataset Information

Introduction and impact of routine whole genome sequencing in the diagnosis and management of sarcoma.

Background

Methods

Results

Conclusion

Publications

Introduction and impact of routine whole genome sequencing in the diagnosis and management of sarcoma.

Similar Datasets

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