A major international collaboration featuring Israeli researchers has concluded the “most comprehensive” study and mapping of cancer genomes to date, boosting global understanding of cancer and its causes.The “unprecedented” Pan-Cancer Analysis of Whole Genomes (PCAWG) project involved more than 1,300 scientists and clinicians from 37 countries, analyzing more than 2,600 genomes – the complete set of genes or genetic material present in a cell or organism – of 38 different tumor types to create a huge resource of primary cancer genomes.A team of scientists from Bar-Ilan University’s Azrieli Faculty of Medicine participated in the project, commonly known as the Pan-Cancer Project, which researchers say significantly improves “fundamental understanding of cancer and signposting [of] new directions for its diagnosis and treatment.” Previous studies to map cancer genomes focused on just 1% of the genome that codes for proteins, which the scientists said is analogous to mapping the coasts of the world’s continents. The Pan-Cancer Project, in contrast, harnesses new technologies to explore the remaining 99% of the genome in greater detail, including key regions that control switching genes on and off – analogous to mapping the interior of continents.Following the completion of the study, the project published its new findings in 23 papers last week in Nature and affiliated journals and has made available a new comprehensive resource for cancer genomics research.Dr. Milana Frenkel-Morgenstern, who headed the team of researchers from Bar-Ilan University, told The Jerusalem Post the “uniformly processed and highly curated sets of all classes of somatic mutations” from thousands of cancer genomes analyzed by the project, combined with most other suitable cancer genomes, present a “unique opportunity to establish the repertoire of mutational signatures and determine their activities across different types of cancer.”The future impact of the project, she said, may be comparable to the “human genome sequencing in 2000,” a major international collaboration to sequence and map all human genes for the first time. The group from Bar-Ilan University led by Frenkel-Morgenstern, Israel’s only representatives in the genomics and transcriptomics studies of the project, participated in two working groups: PAWG-3, tasked with studying the integration of transcriptome and genome; and PAWG-6, which focused on chimeric transcripts and fusion proteins in cancers.“The impact for my team is huge. We received an endless amount of data on cancer genomes, and we have explored the signals already for last seven years of the Pan-Cancer Project,” said Frenkel-Morgenstern, who heads the Cancer Genomics and BioComputing of Complex Diseases Laboratory at the Azrieli Faculty of Medicine.“We plan to extensively apply the Pan-Cancer data sets for our method of chimeric transcripts and gene fusion analyses in order to understand the complexity of chromosomal alterations and trans-splicing in cancer cells,” she said.The team also plans to collaborate with faculty colleagues and researchers from other Israeli institutes to understand the complexity of cancer genomes and transcriptomes. The researchers also intend to collaborate with the Israel Innovation Authority to establish unique Israeli high-performance computing facilities to benefit all researchers in the field.Among its many findings, the project reported that the cancer genome is finite and knowable, even if enormously complicated. Combining sequencing of the whole cancer genome with a series of analysis tools enables researchers to characterize every genetic change found in a cancer and all the processes that generated the mutations. The researchers also said they are close to cataloging all the biological pathways involved in cancer, forming a fuller picture of their actions in the genome.In addition, a new method of carbon dating enabled researchers to identify mutations occurring years, sometimes decades, before the appearance of a tumor. Theoretically, this may open a “window of opportunity” for early cancer detection.“The findings we have shared with the world today are the culmination of an unparalleled, decade-long collaboration that explored the entire cancer genome,” said Dr. Lincoln Stein, a member of the Pan-Cancer Project steering committee and head of adaptive oncology at the Ontario Institute for Cancer Research.“With the knowledge we have gained about the origins and evolution of tumors, we can develop new tools and therapies to detect cancer earlier, develop more targeted therapies and treat patients more successfully,” he said.