title: Molecular inimitability amongst tumors: implications for precision cancer medicine in the age of personalized oncology.
abstract: Tumor sequencing has revolutionized oncology, allowing for detailed interrogation of the molecular underpinnings of cancer at an individual level. With this additional insight, it is increasingly apparent that not only do tumors vary within a sample (tumor heterogeneity), but also that each patient's individual tumor is a constellation of unique molecular aberrations that will require an equally unique personalized therapeutic regimen. We report here the results of 439 patients who underwent Clinical Laboratory Improvement Amendment (CLIA)-certified next generation sequencing (NGS) across histologies. Among these patients, 98.4% had a unique molecular profile, and aside from three primary brain tumor patients with a single genetic lesion (IDH1 R132H), no two patients within a given histology were molecularly identical. Additionally, two sets of patients had identical profiles consisting of two mutations in common and no other anomalies. However, these profiles did not segregate by histology (lung adenocarcinoma-appendiceal cancer (KRAS G12D and GNAS R201C), and lung adenocarcinoma-liposarcoma (CDK4 and MDM2 amplification pairs)). These findings suggest that most advanced tumors are molecular singletons within and between histologies, and that tumors that differ in histology may still nonetheless exhibit identical molecular portraits, albeit rarely.
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Sandip P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Schwaederle
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Daniels
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Fanta
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Schwab
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Shimabukuro
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Piccioni
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Lyudmila A
authors.initials: LA
authors.lastname: Bazhenova
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Helsten
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Parker
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: cancer; clinical trials; genomics; next-generation sequencing; personalized medicine