Researchers from Guangdong Lung Cancer Institute worked with Geneseeq Technology Inc (Geneseeq) performed whole-exome sequencing (WES) on primary tumors and metastases of lung cancer patients to take a closer look at the genomic divergence, metastatic drivers, the timing of metastatic dissemination, and evolutionary origins of the disease.

The study, reported in the Journal of Thoracic Oncology, conducted WES on 187 samples from a cohort of 47 advanced lung cancer patients. By looking into the underlying molecular mechanisms and evolutionary patterns of tumors and metastases, they shed a light on the temporal and spatial pattern of tumor spreading. The researchers found multiple metastasis selected/enriched genetic alterations. To isolate and understand the clonality of the tumors, the team performed multi-region sampling including metastases in the brain, adrenal gland, and bone. They identified genomic alterations that drive metastases, compared the molecular properties of primary and metastasis samples, and then cross-validated the results with an independent cohort from the Memorial Sloan-Kettering Cancer (MSK LUAD) database.

After diligent statistical modeling, they found that 61.1% of the tumors were late dissemination where the metastatic seeding happened around 2.74 years before clinical detection. The only exception was lymph node metastases where the dissemination time was early.

The most frequently mutated genes in the study cohort were TP53, EGFR, KRAS, KEAP1 which mainly contain clonal alterations, and the concordance of the tumorigenic drivers was high between primary and metastasis pairs.

They also searched for metastases-selected genetic features and identified amplification of RICTOR, KDM2A, and NKX2-1, mutations in NPIPA2, WDR87, NPIPA1, C16orf3, and DDX11, as well as chromosomal arm 20p gain and 11p loss, implying the potential importance of these molecular features to drive metastases.

“This study highlights the importance of implementing early cancer detection to minimize metastases” Dr. Hua Bao, the Director of R&D at Geneseeq, author of the study, said in a statement. “We demonstrated that most of the non-lymph node metastases were seeded by the primary tumor, making the detection of primary tumor the utmost priority in preventing death in lung cancer patients.”

Early detection, diagnosis, and treatment of cancer can significantly improve patients’ survival and quality of life. Geneseeq has been dedicated to developing liquid biopsy tests for early cancer detection for the past three years through its MercuryTM program. More tests in this focus area will be made available to patients shortly.