Faculty Collaboration Database

Molecular inimitability amongst tumors: implications for precision cancer medicine in the age of personalized oncology. Oncotarget 2015 Oct 20;6(32):32602-9

Date

09/30/2015

Pubmed ID

26418953

Pubmed Central ID

PMC4741715

DOI

10.18632/oncotarget.5289

Scopus ID

2-s2.0-84946026939 (requires institutional sign-in at Scopus site)   15 Citations

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.

Author List

Patel SP, Schwaederle M, Daniels GA, Fanta PT, Schwab RB, Shimabukuro KA, Kesari S, Piccioni DE, Bazhenova LA, Helsten TL, Lippman SM, Parker BA, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biomarkers, Tumor
Computational Biology
DNA Mutational Analysis
Databases, Genetic
Female
Gene Expression Profiling
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasms
Patient Selection
Phenotype
Precision Medicine
Predictive Value of Tests
Prognosis