Abstract
Purpose: Recent sequencing studies revealed that a subset of colorectal cancer harbors a significantly higher number of somatic mutations. These hypermutated tumors show distinct clinicopathologic features. However, the prognostic impact of the hypermutated tumors is not clearly established. Experimental Design: We analyzed tumor mutation burden (TMB) from targeted next-generation sequencing data of 40 major genes in 516 patients with colorectal cancer. TMB was defined as total number of nonsynonymous mutations per tumor. Cutoff value for TMB-high was chosen by which best discriminated relapse-free survival (RFS) using the Contal and O'Quigley method. Results: In the TCGA data, mutation count of the selected 40 genes reflected the whole exome mutation burden (Pearson correlation ¼ 0.873, P < 0.001). In our patient cohort, 8 or more mutations in the 40 genes was defined as TMB-high, which best discriminated RFS. A total of 55 patients (10.7%) had TMB-high. TMB-high tumors were more frequently found in a proximal location (63.6%) and had a higher proportion of N0 disease (30.9%) and MSI-H (49.1%) compared with TMB-low. Most importantly, TMB-high was associated with better 5-year RFS compared with TMB-low (96.3% vs. 79.8%, P ¼ 0.005). Although there was significant overlap between TMB-high and MSI-H, MSI-H status was not significantly associated with RFS. Multivariate analysis revealed TMB-high as an independent positive prognostic factor for RFS [adjusted HR, 0.16 (95% confidence interval, 0.04-0.66), P ¼ 0.011]. Conclusions: TMB-high is associated with better prognosis in patients with colorectal cancer treated with curative surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy.
| Original language | English |
|---|---|
| Pages (from-to) | 6141-6147 |
| Number of pages | 7 |
| Journal | Clinical Cancer Research |
| Volume | 25 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - 2019 Oct 15 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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Tumor mutation burden and prognosis in patients with colorectal cancer treated with adjuvant fluoropyrimidine and oxaliplatin. / Lee, Dae Won; Han, Sae Won; Bae, Jeong Mo; Jang, Hoon; Han, Hyojun; Kim, Hyoki; Bang, Duhee; Jeong, Seung Yong; Park, Kyu Joo; Kang, Gyeong Hoon; Kim, Tae You.
In: Clinical Cancer Research, Vol. 25, No. 20, 15.10.2019, p. 6141-6147.Research output: Contribution to journal › Article
TY - JOUR
T1 - Tumor mutation burden and prognosis in patients with colorectal cancer treated with adjuvant fluoropyrimidine and oxaliplatin
AU - Lee, Dae Won
AU - Han, Sae Won
AU - Bae, Jeong Mo
AU - Jang, Hoon
AU - Han, Hyojun
AU - Kim, Hyoki
AU - Bang, Duhee
AU - Jeong, Seung Yong
AU - Park, Kyu Joo
AU - Kang, Gyeong Hoon
AU - Kim, Tae You
PY - 2019/10/15
Y1 - 2019/10/15
N2 - Purpose: Recent sequencing studies revealed that a subset of colorectal cancer harbors a significantly higher number of somatic mutations. These hypermutated tumors show distinct clinicopathologic features. However, the prognostic impact of the hypermutated tumors is not clearly established. Experimental Design: We analyzed tumor mutation burden (TMB) from targeted next-generation sequencing data of 40 major genes in 516 patients with colorectal cancer. TMB was defined as total number of nonsynonymous mutations per tumor. Cutoff value for TMB-high was chosen by which best discriminated relapse-free survival (RFS) using the Contal and O'Quigley method. Results: In the TCGA data, mutation count of the selected 40 genes reflected the whole exome mutation burden (Pearson correlation ¼ 0.873, P < 0.001). In our patient cohort, 8 or more mutations in the 40 genes was defined as TMB-high, which best discriminated RFS. A total of 55 patients (10.7%) had TMB-high. TMB-high tumors were more frequently found in a proximal location (63.6%) and had a higher proportion of N0 disease (30.9%) and MSI-H (49.1%) compared with TMB-low. Most importantly, TMB-high was associated with better 5-year RFS compared with TMB-low (96.3% vs. 79.8%, P ¼ 0.005). Although there was significant overlap between TMB-high and MSI-H, MSI-H status was not significantly associated with RFS. Multivariate analysis revealed TMB-high as an independent positive prognostic factor for RFS [adjusted HR, 0.16 (95% confidence interval, 0.04-0.66), P ¼ 0.011]. Conclusions: TMB-high is associated with better prognosis in patients with colorectal cancer treated with curative surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy.
AB - Purpose: Recent sequencing studies revealed that a subset of colorectal cancer harbors a significantly higher number of somatic mutations. These hypermutated tumors show distinct clinicopathologic features. However, the prognostic impact of the hypermutated tumors is not clearly established. Experimental Design: We analyzed tumor mutation burden (TMB) from targeted next-generation sequencing data of 40 major genes in 516 patients with colorectal cancer. TMB was defined as total number of nonsynonymous mutations per tumor. Cutoff value for TMB-high was chosen by which best discriminated relapse-free survival (RFS) using the Contal and O'Quigley method. Results: In the TCGA data, mutation count of the selected 40 genes reflected the whole exome mutation burden (Pearson correlation ¼ 0.873, P < 0.001). In our patient cohort, 8 or more mutations in the 40 genes was defined as TMB-high, which best discriminated RFS. A total of 55 patients (10.7%) had TMB-high. TMB-high tumors were more frequently found in a proximal location (63.6%) and had a higher proportion of N0 disease (30.9%) and MSI-H (49.1%) compared with TMB-low. Most importantly, TMB-high was associated with better 5-year RFS compared with TMB-low (96.3% vs. 79.8%, P ¼ 0.005). Although there was significant overlap between TMB-high and MSI-H, MSI-H status was not significantly associated with RFS. Multivariate analysis revealed TMB-high as an independent positive prognostic factor for RFS [adjusted HR, 0.16 (95% confidence interval, 0.04-0.66), P ¼ 0.011]. Conclusions: TMB-high is associated with better prognosis in patients with colorectal cancer treated with curative surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy.
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UR - http://www.scopus.com/inward/citedby.url?scp=85073313253&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-1105
DO - 10.1158/1078-0432.CCR-19-1105
M3 - Article
C2 - 31285374
AN - SCOPUS:85073313253
VL - 25
SP - 6141
EP - 6147
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 20
ER -