Clinical application of whole-genome sequencing of solid tumors for precision oncology.
Ryul KimSeokhwi KimBrian Baek-Lok OhWoo Sik YuChang Woo KimHoon HurSang-Yong SonMin Jae YangDae Sung ChoTaeyang HaSubin HeoJeon Yeob JangJae Sung YunKyu-Sung KwackJai Keun KimJimi HuhSun Gyo LimSang-Uk HanHyun Woo LeeJi Eun ParkChul-Ho KimJin RohYoung Wha KohDakeun LeeJang-Hee KimGil Ho LeeChoong-Kyun NohYun Jung JungJi Won ParkSeungsoo SheenMi Sun AhnYong Won ChoiTae-Hwan KimSeok Yun KangJin-Hyuk ChoiSoo Yeon BaekKee Myung LeeSun Il KimSung Hyun NohSe-Hyuk KimHyemin HwangEunjung JooShinjung LeeJong-Yeon ShinJi-Young YunJunggil ParkKijong YiYoungoh KwonWon-Chul LeeHansol ParkJoonoh LimBoram YiJaemo KooJune-Young KohSangmoon LeeYuna LeeBo-Rahm LeeErin Connolly-StrongYoung Seok JuMinsuk KwonPublished in: Experimental & molecular medicine (2024)
Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.
Keyphrases
- clinical practice
- clinical trial
- copy number
- papillary thyroid
- single cell
- palliative care
- squamous cell
- randomized controlled trial
- squamous cell carcinoma
- gene expression
- adverse drug
- healthcare
- genome wide
- climate change
- deep learning
- cancer therapy
- hepatitis c virus
- childhood cancer
- lymph node metastasis
- electronic health record
- phase ii
- open label
- human health