L Liu1, J M Toung2, A F Jassowicz3, R Vijayaraghavan2, H Kang2, R Zhang2, K M Kruglyak2, H J Huang3, T Hinoue4, H Shen4, N S Salathia2, D S Hong3, A Naing3, V Subbiah3, S A Piha-Paul3, M Bibikova2, G Granger2, B Barnes2, R Shen2, K Gutekunst2, S Fu3, A M Tsimberidou3, C Lu5, C Eng6, S L Moulder7, E S Kopetz6, R N Amaria8, F Meric-Bernstam3, P W Laird4, J-B Fan2, F Janku9. 1. Illumina, Inc., San Diego, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: lliu3@illumina.com. 2. Illumina, Inc., San Diego, The University of Texas MD Anderson Cancer Center, Houston, USA. 3. Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, USA. 4. Van Andel Research Institute, Grand Rapids, The University of Texas MD Anderson Cancer Center, Houston, USA. 5. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 6. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 7. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 8. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 9. Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: fjanku@mdanderson.org.
Abstract
Background: Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis. Patients and methods: We developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients' outcomes. Results: Median methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P < 0.001) and longer time-to-treatment failure (2.8 versus 1.6 months, P = 0.016). Conclusions: Comprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.
Background: Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis. Patients and methods: We developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients' outcomes. Results: Median methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P < 0.001) and longer time-to-treatment failure (2.8 versus 1.6 months, P = 0.016). Conclusions: Comprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.
Authors: Manny D Bacolod; Aashiq H Mirza; Jianmin Huang; Sarah F Giardina; Philip B Feinberg; Steven A Soper; Francis Barany Journal: J Mol Diagn Date: 2020-05-12 Impact factor: 5.568
Authors: Mohamed A Gouda; Helen J Huang; Sarina A Piha-Paul; S Greg Call; Daniel D Karp; Siqing Fu; Aung Naing; Vivek Subbiah; Shubham Pant; Derek J Dustin; Apostolia M Tsimberidou; David S Hong; Jordi Rodon; Funda Meric-Bernstam; Filip Janku Journal: JCO Precis Oncol Date: 2022-07
Authors: Alexej Ballhausen; Jennifer J Wheler; Daniel D Karp; Sarina A Piha-Paul; Siqing Fu; Shubham Pant; Apostolia M Tsimberidou; David S Hong; Vivek Subbiah; Veronica R Holley; Helen J Huang; Abenaa M Brewster; Kimberly B Koenig; Nuhad K Ibrahim; Funda Meric-Bernstam; Filip Janku Journal: Clin Cancer Res Date: 2020-10-28 Impact factor: 12.531