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AACR Presentation Highlights Potential of Profiling Telomere Alterations in Pediatric Cancers Using WGS Data

By Andrea Anderson

CHICAGO (GenomeWeb News) – Along with the sorts of mutations and structural alterations researchers typically look for in cancer genomes, whole-genome sequence data has the potential for uncovering cancer-related shifts in telomere maintenance, attendees heard during a session on pediatric cancer genomics at the American Association for Cancer Research annual meeting here yesterday.

By searching whole-genome sequence data for reads that contain a characteristic telomere repeat sequence and then looking at how these read counts stack up across the genome in tumor and matched normal samples, researchers are able to figure out which pediatric cancers are prone to telomere amplification or shrinkage, explained St. Jude Children's Research Hospital researcher Matthew Parker.

Parker is participating in the Pediatric Cancer Genome Project, a joint St. Jude-Washington University effort launched in 2010 that aims to genomically characterize 600 tumor-normal samples from pediatric cancer cases over three years. He presented initial findings for around 200 matched tumor-normal pediatric cancer samples from at least nine cancer types that have been assessed for telomere alterations so far.

While past studies have uncovered telomere shortening in certain adult cancers, Parker said he and his colleagues are finding the opposite pattern in a subset of the pediatric cancer types they've tested for telomere alterations so far.

Although the team has found typical telomere lengths in tumors from around half a dozen pediatric cancer types, others appear to be prone to telomere lengthening, including osteosarcoma, adrenocortical carcinoma, and neuroblastoma.

Moreover, Parker noted that the presence of longer telomeres in these tumors often appears to coincide with the presence of extensive somatic structural variation in general or with mutations affecting a specific gene.

For example, in a PCGP study published in the Journal of the American Medical Association last month, the group found that the majority of neuroblastoma tumors harboring age-of-diagnosis-associated mutations or structural variations in the ATRX gene also had longer-than-usual telomeres.

The researchers still have more pediatric tumors to test. But based on their findings so far, they believe that genome-wide telomere length patterns will add a valuable new layer of information when trying to interpret pediatric cancer genomes.

"These data suggest that some pediatric cancers are associated with marked abnormalities in telomere maintenance leading to expansion in the telomere repeats," Parker and his colleagues wrote in the presentation's abstract.

"Defining the specific mutational processes that are responsible for these telomere defects and expanding the dataset to all 600 cancers in the project should help to define the mechanisms through which these alterations contribute to the transformed phenotypes."

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