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The Utility and Relevance of Comprehensive Genomic Profiling in Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 3339

Special Issue Editor


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Guest Editor
Chi Mei Medical Center/National Institute of Cancer Research, National Health Research Institutes, Tainan 367, Taiwan
Interests: urothelial cancer; sarcoma; molecular pathology; experimental therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the past, surgery was the mainstay of solid tumor in its early stage, and chemotherapy and experimental therapies were the therapeutic cornerstones in unresectable and metastatic lesions. However, recent advances in next-generation-sequencing-based genomic profiling has dramatically hastened the disclosure of the biological and immune landscapes of cancer, leading to the development of potential biomarkers carrying prognostic and/or therapeutic relevance. The application of whole-genome/exome sequencing or well-designed comprehensive genomic profiling not only confers an opportunity for more precise cancer diagnosis, but also more individualized therapeutics. Moreover, it is also helpful in the accumulation of cancer genomic datasets to allow integrative analysis on various molecular profiling for the identification of distinct molecular/histological subtypes of cancers with diverse clinical behaviors and potential sensitivity to various therapies. It has also led to the disclosure of frequently altered genes and proteins that could lead to the perturbation of intracellular signaling pathways and their microenvironment. In the present Issue, we aim to determine the most up-to-date advances driven by comprehensive genomic profiling in the field of molecular diagnostics and theranostics.

Prof. Dr. Chien-Feng Li
Guest Editor

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Keywords

  • cancer
  • carcinoma
  • sarcoma
  • next-generation sequencing
  • genomic
  • mutation
  • fusion

Published Papers (1 paper)

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Review

12 pages, 422 KiB  
Review
Open the Technical Black Box of Tumor Mutational Burden (TMB): Factors Affecting Harmonization and Standardization of Panel-Based TMB
by Meng-Ta Sung, Yeh-Han Wang and Chien-Feng Li
Int. J. Mol. Sci. 2022, 23(9), 5097; https://doi.org/10.3390/ijms23095097 - 03 May 2022
Cited by 5 | Viewed by 2564
Abstract
As tumor mutational burden (TMB) has been approved as a predictive biomarker for immune checkpoint inhibitors (ICIs), next-generation sequencing (NGS) TMB panels are being increasingly used clinically. However, only a few of them have been validated in clinical trials or authorized by administration. [...] Read more.
As tumor mutational burden (TMB) has been approved as a predictive biomarker for immune checkpoint inhibitors (ICIs), next-generation sequencing (NGS) TMB panels are being increasingly used clinically. However, only a few of them have been validated in clinical trials or authorized by administration. The harmonization and standardization of TMB panels are thus essential for clinical implementation. In this review, preanalytic, sequencing, bioinformatics and interpretative factors are summarized to provide a comprehensive picture of how the different factors affect the estimation of panel-based TMB. Among the factors, poor DNA quality, improper formalin fixation and residual germline variants after filtration may overestimate TMB, while low tumor purity may decrease the sensitivity of the TMB panel. In addition, a small panel size leads to more variability when comparing with true TMB values detected by whole-exome sequencing (WES). A panel covering a genomic region of more than 1Mb is more stable for harmonization and standardization. Because the TMB estimate reflects the sum of effects from multiple factors, deliberation based on laboratory and specimen quality, as well as clinical information, is essential for decision making. Full article
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