Research Associate, RD, Gene Solutions
University of Queensland, Australia. Immunology & Genetics
We previously developed a multimodal ctDNA assay, Screening for the Presence of Tumor by Methylation And Size (SPOT-MAS), designed to profile methylation and fragmentomic signatures for multi-cancer early detection. SPOT-MAS has demonstrated its capability to capture ctDNA signatures from 05 common cancer types—breast, lung, liver, colorectal, and gastric cancer—and successfully facilitated early-stage detection in both retrospective (4) and prospective validation (5) studies.
This study extends the analysis to the 05 lethal LSS cancers: endometrial, esophageal, head and neck, ovarian and pancreatic.
In this study, 739 healthy individuals and 135 patients with one of five LSS cancer types (endometrial, esophageal, head and neck, ovarian, and pancreatic) were recruited from 15 hospitals between May 2023 and July 2024. Healthy participants were monitored for 12 months to confirm their cancer-free status, while cancer diagnoses were confirmed histologically for all patients. The cancer group (median age 60) was significantly older than the control group (median age 47), with similar gender distribution overall, though ovarian and endometrial cancers occurred exclusively in females, and esophageal and head and neck cancers were mostly in males. Most cancer patients (79.3%) were diagnosed at advanced stages (III and IV).
End motifs: Additionally, specific 4-mer end motifs were identified as significant for distinguishing ctDNA from different cancer types, with 11 shared motifs across all five cancers.
These methylation, fragment length, and motif end changes in cfDNA could serve as potential biomarkers for detecting LSS cancers that currently lack standard screening options.
The study investigated whether ctDNA signatures from LSS cancers overlap with those from the five most common cancers (breast, colorectal, lung, liver, and prostate). Significant shared methylation patterns were found in esophageal, head and neck, and pancreatic cancers, with over 1,000 overlapping methylation bins identified across four LSS cancers (excluding endometrial cancer). Additionally, shared fragment length changes and end motifs were observed across all five LSS cancers. Chromosomal copy number alterations (CNA) common to LSS and common cancers were detected, with notable differences in endometrial cancer.
(1) Hackshaw A, Cohen SS, Reichert H, et al. Estimating the population health impact of a multi-cancer early detec- tion genomic blood test to complement existing screen- ing in the US and UK. Br J Cancer. 2021;125(10):1432– 1442. doi:10.1038/s41416-021-01498-4
(2) Kurjak A, Shalan H, Kupesic S, et al. An attempt to screen asymptomatic women for ovarian and endometrial can- cer with transvaginal color and pulsed Doppler sonogra- phy. J Ultrasound Med. 1994;13(4):295–301. doi:10.7863/ jum.1994.13.4.295
(3) WHO, American Cancer Society 2024 and USPSTF recommendations
(4) Le Son Tran et al. Analytical and clinical validation of a circulating tumor DNA–based assay for multicancer early detection.. JCO 42, 10548- 10548(2024).DOI:10.1200/JCO.2024.42.16_suppl.10548
(5) Nguyen, H., Luong, B. A., Tran, D., Nguyen, T., Ngo, Q. D., Le, L. G. H., Ho, Q. C., Nguyen, H. T., Nguyen, C. M., Tran, V. U., Pham, T. V. N., Le, M. T., Le, N. a. T., Le, T. K., Nguyen, T. L., Pham, H. T., Le, H. T., Duong, H. D. T., Hoang, A. V., . . . Tran, D. T. (2021). Ultra-Deep Sequencing of Plasma-Circulating DNA for the Detection of Tumor- Derived Mutations in Patients with Nonmetastatic Colorectal Cancer. Cancer In vestigation, 40(4), 354–365. https://doi.org/10.1080/07357907.2021.2017951
Request the test through your primary care doctor. A prescription and 10ml blood collection are required.
Your extracted DNA from the plasma will be sequenced by Next–generation ctDNA technology to analyze methylation profile and multi–feature of DNA.
Receive your ctDNA signal analysis results after 20 working days from the time sample is received at Gene Solutions Genomics Singapore laboratory.