Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer
| Autor: | Kai Wang, Juliann Chmielecki, Deborah Morosini, Gary A. Palmer, Doron Lipson, Siraj M. Ali, Christine E. Sheehan, V.A. Miller, J.A. Elvin, L Foulke, Phillip J. Stephens, J.S. Ross, Osama El-Kadi, G. Otto, Ashley J Tarasen, Roman Yelensky |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Lung Neoplasms Disease Biology medicine.disease_cause Bioinformatics Pathology and Forensic Medicine Molecular Genetics Breast cancer Predictive Value of Tests Internal medicine medicine Biomarkers Tumor PTEN Humans Genetic Predisposition to Disease Genetic Testing Precision Medicine Lung cancer neoplasms Aged Retrospective Studies Aged 80 and over Gene Expression Profiling Patient Selection Lung Cancer High-Throughput Nucleotide Sequencing Retrospective cohort study Cell Differentiation General Medicine Middle Aged medicine.disease Prognosis Small Cell Lung Carcinoma respiratory tract diseases Gene expression profiling Molecular Oncology Phenotype Predictive value of tests biology.protein Original Article Female KRAS Molecular Pathology |
| Zdroj: | Journal of Clinical Pathology |
| ISSN: | 1472-4146 0021-9746 |
| Popis: | AimsSmall cell lung cancer (SCLC) carries a poor prognosis, and the systemic therapies currently used as treatments are only modestly effective, as demonstrated by a low 5-year survival at only ∼5%. In this retrospective collected from March 2013 to study, we performed comprehensive genomic profiling of 98 small cell undifferentiated lung cancer (SCLC) samples to identify potential targets of therapy not currently searched for in routine clinical practice.MethodsDNA from 98 SCLC was sequenced to high, uniform coverage (Illumina HiSeq 2500) and analysed for all classes of genomic alterations.ResultsA total of 386 alterations were identified for an average of 3.9 alterations per tumour (range 1–10). Fifty-two (53%) of cases harboured at least 1 actionable alteration with the potential to personalise therapy including base substitutions, amplifications or homozygous deletions in RICTOR (10%), KIT (7%), PIK3CA (6%), EGFR (5%), PTEN (5%), KRAS (5%), MCL1 (4%), FGFR1 (4%), BRCA2, (4%), TSC1 (3%), NF1 (3%), EPHA3 (3%) and CCND1. The most common non-actionable genomic alterations were alterations in TP53 (86% of SCLC cases), RB1 (54%) and MLL2 (17%).ConclusionsGreater than 50% of the SCLC cases harboured at least one actionable alteration. Given the limited treatment options and poor prognosis of patients with SCLC, comprehensive genomic profiling has the potential to identify new treatment paradigms and meet an unmet clinical need for this disease. |
| Databáze: | OpenAIRE |
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