PMID- 31502147
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20221207
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 2055
DP  - 2020
TI  - Measuring Tumor Mutational Burden Using Whole-Exome Sequencing.
PG  - 63-91
LID - 10.1007/978-1-4939-9773-2_3 [doi]
AB  - Cancer immunotherapy, particularly a class of antibodies targeting the CTLA4 and 
      PD-1/PD-L1 negative regulators of immune response (collectively called the immune 
      checkpoint), is one of the most promising approaches for cancer treatment and the 
      use of immune checkpoint inhibitors (ICI) has demonstrated remarkable success in 
      several types of cancer. In studies of unselected patient populations, it was 
      shown that melanoma, non small cell lung cancer (NSCLC), renal cell carcinoma and 
      urothelial carcinoma patients treated with CTLA-4, PD-1 or PD-L1 inhibitors had 
      an improved objective response and overall survival relative to chemotherapy or 
      historical trends, and several ICIs have been approved for the treatment of these 
      and other indications.More recently, several groups found that response to ICI 
      therapy strongly correlates with a high burden of single nucleotide variant (SNV) 
      mutations in the tumor genome, termed tumor mutational burden (TMB), usually 
      expressed as the number of nonsynonymous single nucleotide variants per megabase 
      of sequenced genome. These studies showed that TMB is a promising predictive 
      biomarker for ICI response in melanoma, urothelial carcinoma and a subset of 
      NSCLC patients. High TMB relates to ICI response via the production of increased 
      numbers of novel, mutant peptide antigens (neoantigens), resulting in enhanced 
      recognition and killing of neoantigen-presenting tumor cells by cytotoxic CD8+ T 
      cells.In this chapter I describe the current best-practice methods for measuring 
      TMB in tumor specimens using whole-exome sequencing (WES).
FAU - Vilimas, Tomas
AU  - Vilimas T
AD  - Molecular Characterization Laboratory, Frederick National Laboratory for Cancer 
      Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. 
      tomas.vilimas@nih.gov.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Antineoplastic Agents, Immunological/pharmacology/therapeutic use
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Gene Regulatory Networks/drug effects
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - *Mutation
MH  - Neoplasms/drug therapy/*genetics/immunology
MH  - Exome Sequencing/*methods
OTO - NOTNLM
OT  - Cancer immunotherapy biomarker
OT  - Immune checkpoint inhibitor
OT  - Neoantigens
OT  - Next-generation sequencing
OT  - Nonsynonymous mutations
OT  - Tumor mutational burden
OT  - Whole-exome sequencing
EDAT- 2019/09/11 06:00
MHDA- 2020/11/11 06:00
CRDT- 2019/09/11 06:00
PHST- 2019/09/11 06:00 [entrez]
PHST- 2019/09/11 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
AID - 10.1007/978-1-4939-9773-2_3 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2020;2055:63-91. doi: 10.1007/978-1-4939-9773-2_3.