Clinical OMICS

MAR-APR 2018

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 8 of 51 March/April 2018 Clinical OMICs 7 is too costly to do 500x coverage with whole-genome sequencing. This could also reduce the price of sequencing as well as improve the success rates." After a study found FFPE whole genome sequencing via SeqPlus to generate similar call data to fresh frozen samples—using measures that included allele frequency and heterozygous to homozygous call ratio—WuXi NextCODE then tested its method through the largest-to-date study of FFPE samples. The company sequenced 516 pairs of sample tissue—one tumor and one normal per pair. The tumor samples, which were sequenced at a targeted depth of 70x, demonstrate average coverages of 99% and 98% at 10x and 20x, respectively. The paired normal tissue samples, which were sequenced at a lower targeted depth of 30X, demonstrated average coverages of 98.1% and 92.6% at 10x and 20x, respectively. Both of these samples demonstrate data comparable to the fresh-frozen controls. 10 to 15 Med Center Partnerships Gulcher anticipates WuXi Next- CODE will work with at least 10 to 15 different academic medical cen- ters to help it collect a critical mass of pertinent data. "I don't think it's going to be as simple as being able to use just one medical center for a given cancer. We're probably going to have to use two or three medical centers, just to get enough samples for human can- cer for the matched metastatic vs primary tumor projects. With some centers, we'll work with certain can- cer types. With others, we'll work with different cancer types, depend- ing on their expertise." In some of WuXi NextCODE's part- nerships, he added, the medical cen- ters use the company's tools to access the cancer datasets of The Cancer Genome Atlas (TCGA), which houses data from approximately 11,000 patients and 33 cancer types, after gaining permission from the NCI. One such tool is the Tumor Mutation Analyzer (TMA), designed to provide a fast, intuitive and visual means of analyzing and comparing next-gener- ation sequence data from tumor-nor- mal pairs and tumor cohorts. TMA simultaneously integrates the MuTect algorithm from the Broad Insti- tute, and the VarScan2 algorithm of Washington University in St. Louis, to pick out the most promising variants. TMA uses the company's Genomically Ordered Relational (GOR) database architecture, and is fully integrated with its germline Clinical Sequence Analyzer and Sequence Miner. WuXi NextCODE will work with the multiple medical centers to gain insights into how primary tumors WuXi NextCODE CSO Jeffrey Gulcher Smita Jacob for WuXi NextCODE Melanoma Mutation Hides in Tumor, Poised to Thwart Treatment A rare resistance mutation first thought to appear in melanoma following treat- ment with a targeted therapy has instead turned out to be hiding in the tumor all along, poised to stop the treatment in its tracks before it could begin, according to a recent study. Lawrence Kwong, Ph.D., assistant pro- fessor of translational molecular patholo- gy at The University of Texas MD Anderson Cancer Center, led a research team that set out to find resistance mechanisms against a combination of MEK and CDK4 inhibi- tors designed to treat melanoma that has a mutation in the NRAS gene. The mutation to the PIK3CA gene initial- ly appeared to be an acquired resistance variation arising after treatment. But by re-analyzing the pretreatment biopsy, Kwong and colleagues were able to estab- lish that it was rare but present from the start, hiding on one side of the tumor. The researchers published their findings March 1 in the journal Cancer Discovery. "Our study is the first to measure multi- ple regions in pre-treatment tumor biop- sies at high resolution and then track the resistant mutation over years of treatment through six biopsies," Kwong said in a state- ment. "We are able to say that this mutation started out rare and then rapidly expand- ed as the MEK/CDK4 inhibitors killed off a large number of non-resistant cells. n (continued on next page) STEVE GSCHMEISSNER / SCIENCE PHOTO LIBRARY / Getty Images

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