ATYPICAL RESPONDERS LANDSCAPE REVIEW ∙ OCTOBER, 2017 33 STUDYOR INSTITUTE TYPEOFSAMPLECOLLECTED FORANALYSIS TYPEOFANALYSIS ANALYSISOUTPUT NCI Study: MolecularProfiling inTissueSamples FromPatients WithCancerWho AreExceptional Respondersto Treatments Tumortissuepriortotreatment; normaltissue Wholeexomesequencing. Targeted next-generation deepsequencing will beperformedifsufficient quantitiesof nucleicacidsareavailable. Otheranalyses includemRNA sequencing; microRNA sequencing; wholegenomesequencing; promotermethylation analysis; SNP genotyping “Molecularfeatures” of the exceptional response TheBroad Institute’sMBC Project Tumorbiopsy,saliva,and potentiallybloodsamples Genomicanalysis Shareddatacontainingde-identified genomicandmedicalinformation AURORA(Aiming toUnderstand theMolecular Aberrationsin MetastaticBreast Cancer) Primarytumor;metastatic lesions;blood;serum;plasma Wholeexomesequencing “Biomarkersofresponse and/or resistancetosystemic therapy” Universityof Wisconsin- Madison’s Exceptional SurvivorsStudy Bloodorsaliva,plustumor samplesinasubsetofpatients. Notably,questionnaires regardinglifestyleandother factorswillbeansweredbyall patients. Whole-exomesequencing;questionnaires In asubset ofpatients,the team will lookforgenetic mutations and/ orchangesin gene expressionthat arecommon among“exceptional survivors”andnotfoundin establishedorpublishedsamples from“normal survivors”.The teamwill analyzegermline and tumorgenomics,as wellas tumor- infiltrating immune cells.Responses topatient questionnaires willbe assessed. MemorialSloan KetteringCancer Center TumorDNA MSK-IMPACTTM (genomicsequencing of ~410cancergenes) Clinicallyactionable molecular aberrations; candidates forbasket trials TABLE 2 CURRENT INITIATIVES STUDYING ATYPICAL RESPONSES