Surveying Genomic Landscapes in the Clinical Laboratory: DNA Views of Tumor Terrain

A web search for the term ‘genomic landscapes’ brings up a surprising number of publications from esteemed journals such as Cell, Science, and Nature Genetics. At first glance it would seem that the words ‘genomic’ and ‘landscape’ do not belong together. However, review of the many ‘genomic landscape’ publications from the past decade reveals a recurring theme of tumor DNA testing to survey the terrain of human cancer. Within the peaks and valleys of a tumor genome are amplifications and deletions of specific genes that drive tumorigenesis, fuel local recurrence, and promote distant metastases. Amplification (extra copies) of an oncogene such as human epidermal growth factor receptor 2 (HER2) can drive tumor growth by promoting cell division, cell longevity, and formation of new blood vessels. Deletion (loss of one or both copies) of tumor protein 53 (TP53) or other tumor suppressors, makes normal cells vulnerable to DNA replication errors. Cells that cannot repair or eliminate defective DNA are launched on a path towards cancer.

A DNA view of a lung cancer genome from the PacificDx Laboratory reveals the tumor’s unique landscape of peaks and valleys.

Within the peaks and valleys of this patient’s tumor genome landscape, are potential therapeutic targets including MET gene amplification (red arrow), a positive biomarker for response to anti-MET therapy. MET amplification was confirmed using a precisely targeted, fluorescently labeled DNA probe (orange) to calculate the average number of MET gene copies in the tumor genome nucleus.

Genome Landscapes (instead of single gene testing) allow multiple genes to be analyzed simultaneously from the same tissue sample! The good news is Genomic Landscape testing is a clinically available and affordable option for any cancer patient when the limited view, single gene testing commonly performed at the time of diagnosis does not identify therapeutic targets.

Identification of gene copy number alterations (CNAs) in an individual patient’s tumor is thus increasingly relevant as a growing number of gene deletions and amplifications are used to identify patients who may be eligible for NCCN designated emerging targeted agents.