Next generation sequencing demonstrates association between tumor suppressor gene aberrations and poor outcome in patients with cancer
| Autor: | Santosh Kesari, Maria Schwaederle, Razelle Kurzrock, Barbara A. Parker, Richard Schwab, David Piccioni, Paul T. Fanta, Kelly A. Shimabukuro, Gregory A. Daniels |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Oncology
Male PTEN Time Factors Kaplan-Meier Estimate patient's outcome Bioinformatics Metastasis CDKN2A Neoplasms 2.1 Biological and endogenous factors Genes Tumor Suppressor TP53 Neoplasm Metastasis Precision Medicine biology High-Throughput Nucleotide Sequencing Middle Aged Regression Analysis Female medicine.medical_specialty Tumor suppressor gene tumor suppressor Adenomatous Polyposis Coli Protein Internal medicine Report medicine Humans cancer Molecular Biology Proportional hazards model Tumor Suppressor Proteins PTEN Phosphohydrolase Cancer Histology Cell Biology medicine.disease Precision medicine APC Patient Outcome Assessment Genes biology.protein next-generation sequencing Biochemistry and Cell Biology Tumor Suppressor Protein p53 Digestive Diseases Developmental Biology |
| Zdroj: | Cell cycle (Georgetown, Tex.), vol 14, iss 11 Schwaederle, M; Daniels, GA; Piccioni, DE; Kesari, S; Fanta, PT; Schwab, RB; et al.(2015). Next generation sequencing demonstrates association between tumor suppressor gene aberrations and poor outcome in patients with cancer. Cell Cycle, 14(11), 1730-1737. doi: 10.1080/15384101.2015.1033596. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/5sd09610 Cell Cycle |
| DOI: | 10.1080/15384101.2015.1033596. |
| Popis: | Next generation sequencing is transforming patient care by allowing physicians to customize and match treatment to their patients’ tumor alterations. Our goal was to study the association between key molecular alterations and outcome parameters. We evaluated the characteristics and outcomes (overall survival (OS), time to metastasis/recurrence, and best progression-free survival (PFS)) of 392 patients for whom next generation sequencing (182 or 236 genes) had been performed. The Kaplan-Meier method and Cox regression models were used for our analysis, and results were subjected to internal validation using a resampling method (bootstrap analysis). In a multivariable analysis (Cox regression model), the parameters that were statistically associated with a poorer overall survival were the presence of metastases at diagnosis (P = 0.014), gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001), and CDKN2A alterations (P = 0.0001). The variables associated with a shorter time to metastases/recurrence were gastrointestinal histology (P = 0.004), APC (P = 0.008), PTEN (P = 0.026) and TP53 (P = 0.044) alterations. TP53 (P = 0.003) and PTEN (P = 0.034) alterations were independent predictors of a shorter best PFS. A personalized treatment approach (matching the molecular aberration with a cognate targeted drug) also correlated with a longer best PFS (P = 0.046). Our study demonstrated that, across diverse cancers, anomalies in specific tumor suppressor genes (PTEN, CDKN2A, APC, and/or TP53) were independently associated with a worse outcome, as reflected by time to metastases/recurrence, best PFS on treatment, and/or overall survival. These observations suggest that molecular diagnostic tests may provide important prognostic information in patients with cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|