Dataset Information

Frequent post-operative monitoring of colorectal cancer using individualised ctDNA validated by multiregional molecular profiling.

ABSTRACT:

Background

Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge.

Methods

We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples.

Results

"Founder" mutations, defined as a mutation that is present in all regions of the tumour in a binary manner (i.e., present or absent), were identified in 12/14 tumours. In contrast, "truncal" mutations, which are the first mutation that occurs prior to the divergence of branches in the phylogenetic tree using variant allele frequency (VAF) as continuous variables, were identified in 12/14 tumours. Two tumours without founder and truncal mutations were hypermutators. Most founder and truncal mutations exhibited higher VAFs than "non-founder" and "branch" mutations, resulting in a high chance to be detected in ctDNA. In post-operative long-term observation for 10/12 patients, early relapse prediction, treatment efficacy and non-relapse corroboration were achievable from frequent ctDNA monitoring.

Conclusions

A single biopsy is sufficient to develop custom dPCR probes for monitoring tumour burden in most CRC patients. However, it may not be effective for those with hypermutated tumours.

SUBMITTER: Yaegashi M

PROVIDER: S-EPMC8076308 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Frequent post-operative monitoring of colorectal cancer using individualised ctDNA validated by multiregional molecular profiling.

Yaegashi Mizunori M Iwaya Takeshi T Sasaki Noriyuki N Fujita Masashi M Ju Zhenlin Z Siwak Doris D Hachiya Tsuyoshi T Sato Kei K Endo Fumitaka F Kimura Toshimoto T Otsuka Koki K Sugimoto Ryo R Sugai Tamotsu T Liotta Lance L Lu Yiling Y Mills Gordon B GB Nakagawa Hidewaki H Nishizuka Satoshi S SS

British journal of cancer 20210303 9

<h4>Background</h4>Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge.<h4>Methods</h4>We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples.<h4>Results</h4>"Founder" mutations, defined as a mutation that is ...[more]

PMID: 33658639

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Dataset Information

Frequent post-operative monitoring of colorectal cancer using individualised ctDNA validated by multiregional molecular profiling.

Background

Methods

Results

Conclusions

Publications

Frequent post-operative monitoring of colorectal cancer using individualised ctDNA validated by multiregional molecular profiling.

Similar Datasets

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