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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cancer
2018 ; 9
(13
): 2302-2307
Nephropedia Template TP
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English Wikipedia
The Tumor Mutational Burden of Chinese Advanced Cancer Patients Estimated by a
381-cancer-gene Panel
#MMPMID30026825
Zhuang W
; Ma J
; Chen X
; Wang G
; Lu J
; Chen Y
; Dong H
; Cai S
; Zhang Y
; Zhao X
; Zhu Y
; Xu C
; Huang Y
; Huang Z
; Zhu X
; Jiang H
; Wang Z
J Cancer
2018[]; 9
(13
): 2302-2307
PMID30026825
show ga
Purpose: Tumor mutational burden (TMB) calculated by whole-exome sequencing (WES)
is proved to be effective to predict the clinical benefit of immune checkpoint
blockades. However, WES is not commonly used in China. We aimed to determine if a
381-caner-gene panel (CGP) could be used to estimate TMB, delineate the landscape
of TMB of Chinese patients and identify mutated genes and pathways related to
higher TMB. Methods: We first evaluated the correlation between the TMB estimated
by a 381-cancer-gene panel MasterView and WES using the data from the melanoma
sample cohort. 3023 formalin fixed, paraffin-embedded tumor specimens from 2932
Chinese patients with advanced solid tumor were profiled for 381 gene sequencing,
the baits of which covered 4,557 exons of 365 cancer-related genes and 47 introns
of 25 genes frequently rearranged in cancer (All performed in a lab who achieved
full marks five times in the external quality assessment by College of American
Pathologists [CAP]). Using the sequencing data, we estimated the TMB of Chinese
advanced solid tumor and identified mutated genes and pathways related to higher
TMB level. Results: 381-CGP-mutational burden was strongly associated with those
calculated by WES (R(2) = 0.978). The median TMB for each tumor type was 5.65
(colorectal cancer), 4.84 (lung cancer), 4.03 (hepatobiliary cancer), 4.03
(gastric carcinoma), 4.03 (breast cancer) mutations/mb respectively. No
correlation was observed between TMB level and age (P = 0.577) or gender (P =
0.307). The TMB of patients with mismatch repair (MMR) or DNA repair response
(DDR) pathway deficiency was significantly higher than that without MMR or DDR
pathway deficiency (P < 0.001). Conclusion: The 381-cancer gene panel is a
clinical practicable method to assess tumor mutational burden compared with whole
exome sequencing. MMR and DDR deficiency are correlated with higher tumor
mutational burden of Chinese patients with advanced solid tumors.