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Article

Whole Exome Sequencing of Multi-Regional Biopsies from Metastatic Lesions to Evaluate Actionable Truncal Mutations Using a Single-Pass Percutaneous Technique

1
Department of Haematology-Oncology, National University Cancer Institute, Singapore 119074, Singapore
2
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
3
Department of Radiology, National University Hospital, Singapore 119074, Singapore
4
Department of Pathology, National University of Singapore, Singapore 119077, Singapore
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Cancers 2020, 12(6), 1599; https://doi.org/10.3390/cancers12061599
Received: 17 April 2020 / Revised: 27 May 2020 / Accepted: 7 June 2020 / Published: 17 June 2020
(This article belongs to the Special Issue Precision Medicine in Solid Tumors)
We investigate the feasibility of obtaining multiple spatially-separated biopsies from a single lesion to explore intratumor heterogeneity and identify actionable truncal mutations using whole exome sequencing (WES). A single-pass radiologically-guided percutaneous technique was used to obtain four spatially-separated biopsies from a single metastatic lesion. WES was performed to identify putative truncal variants (PTVs), defined as a non-synonymous somatic (NSS) variant present in all four spatially separated biopsies. Actionable truncal mutations—filtered using the FoundationOne panel—were defined as clinically relevant PTVs. Mutational landscapes of each biopsy and their association with patient outcomes were assessed. WES on 50 biopsied samples from 13 patients across six cancer types were analyzed. Actionable truncal mutations were identified in 9/13 patients; 31.1 ± 5.12 more unique NSS variants were detected with every additional multi- region tumor biopsy (MRTB) analyzed. The number of PTVs dropped by 16.1 ± 17.9 with every additional MRTB, with the decrease most pronounced (36.8 ± 19.7) when two MRTB were analyzed compared to one. MRTB most reliably predicted PTV compared to in silico analysis of allele frequencies and cancer cell fraction based on one biopsy sample. Three patients treated with actionable truncal mutation-directed therapy derived clinical benefit. Multi-regional sampling for genomics analysis is feasible and informative to help prioritize precision-therapy strategies. View Full-Text
Keywords: intratumor heterogeneity; multiple biopsies; tumor evolution; clonality classification; strategic therapeutic intervention intratumor heterogeneity; multiple biopsies; tumor evolution; clonality classification; strategic therapeutic intervention
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MDPI and ACS Style

Heong, V.; Tay, D.; Goh, S.E.; Wee, B.; Tan, T.Z.; Soo, R.; Pang, B.; Lim, D.; Gopinathan, A.; Ow, S.; Chee, C.E.; Goh, B.C.; Lee, S.C.; Yong, W.P.; Wong, A.; Omar, M.F.M.; Soong, R.; Tan, D.S. Whole Exome Sequencing of Multi-Regional Biopsies from Metastatic Lesions to Evaluate Actionable Truncal Mutations Using a Single-Pass Percutaneous Technique. Cancers 2020, 12, 1599. https://doi.org/10.3390/cancers12061599

AMA Style

Heong V, Tay D, Goh SE, Wee B, Tan TZ, Soo R, Pang B, Lim D, Gopinathan A, Ow S, Chee CE, Goh BC, Lee SC, Yong WP, Wong A, Omar MFM, Soong R, Tan DS. Whole Exome Sequencing of Multi-Regional Biopsies from Metastatic Lesions to Evaluate Actionable Truncal Mutations Using a Single-Pass Percutaneous Technique. Cancers. 2020; 12(6):1599. https://doi.org/10.3390/cancers12061599

Chicago/Turabian Style

Heong, Valerie, Darwin Tay, Shane E. Goh, Bernard Wee, Tuan Z. Tan, Ross Soo, Brendan Pang, Diana Lim, Anil Gopinathan, Samuel Ow, Cheng E. Chee, Boon C. Goh, Soo C. Lee, Wei P. Yong, Andrea Wong, Mohamed F.M. Omar, Richie Soong, and David S. Tan. 2020. "Whole Exome Sequencing of Multi-Regional Biopsies from Metastatic Lesions to Evaluate Actionable Truncal Mutations Using a Single-Pass Percutaneous Technique" Cancers 12, no. 6: 1599. https://doi.org/10.3390/cancers12061599

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