We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Clinical application of genomic profiling to find druggable targets for adolescent and young adult (AYA) cancer patients with metastasis.
- Authors
Soojin Cha; Jeongeun Lee; Jong-Yeon Shin; Ji-Yeon Kim; Sung Hoon Sim; Keam, Bhumsuk; Tae Min Kim; Dong-Wan Kim; Dae Seog Heo; Se-Hoon Lee; Jong-Il Kim; Cha, Soojin; Lee, Jeongeun; Shin, Jong-Yeon; Kim, Ji-Yeon; Sim, Sung Hoon; Kim, Tae Min; Kim, Dong-Wan; Heo, Dae Seog; Lee, Se-Hoon
- Abstract
<bold>Background: </bold>Although adolescent and young adult (AYA) cancers are characterized by biological features and clinical outcomes distinct from those of other age groups, the molecular profile of AYA cancers has not been well defined. In this study, we analyzed cancer genomes from rare types of metastatic AYA cancers to identify driving and/or druggable genetic alterations.<bold>Methods: </bold>Prospectively collected AYA tumor samples from seven different patients were analyzed using three different genomics platforms (whole-exome sequencing, whole-transcriptome sequencing or OncoScan™). Using well-known bioinformatics tools (bwa, Picard, GATK, MuTect, and Somatic Indel Detector) and our annotation approach with open access databases (DAVID and DGIdb), we processed sequencing data and identified driving genetic alterations and their druggability.<bold>Results: </bold>The mutation frequencies of AYA cancers were lower than those of other adult cancers (median = 0.56), except for a germ cell tumor with hypermutation. We identified patient-specific genetic alterations in candidate driving genes: RASA2 and NF1 (prostate cancer), TP53 and CDKN2C (olfactory neuroblastoma), FAT1, NOTCH1, and SMAD4 (head and neck cancer), KRAS (urachal carcinoma), EML4-ALK (lung cancer), and MDM2 and PTEN (liposarcoma). We then suggested potential drugs for each patient according to his or her altered genes and related pathways. By comparing candidate driving genes between AYA cancers and those from all age groups for the same type of cancer, we identified different driving genes in prostate cancer and a germ cell tumor in AYAs compared with all age groups, whereas three common alterations (TP53, FAT1, and NOTCH1) in head and neck cancer were identified in both groups.<bold>Conclusion: </bold>We identified the patient-specific genetic alterations and druggability of seven rare types of AYA cancers using three genomics platforms. Additionally, genetic alterations in cancers from AYA and those from all age groups varied by cancer type.
- Subjects
CANCER genetics; CANCER in adolescence; CANCER in young adults; EXOMES; GENOMICS; PROSTATE cancer &; genetics; PROTEIN metabolism; AGE distribution; ANTINEOPLASTIC agents; CELL receptors; CELLULAR signal transduction; DRUG therapy; CHROMOSOME abnormalities; COMPARATIVE studies; DRUG design; GENETIC polymorphisms; GENOMES; RESEARCH methodology; MEDICAL cooperation; GENETIC mutation; PROTEINS; RESEARCH; TUMORS; BIOINFORMATICS; EVALUATION research; GENE expression profiling; SEQUENCE analysis; PHARMACODYNAMICS
- Publication
BMC Cancer, 2016, Vol 16, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-016-2209-1