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BMC Cancer. 2016 Feb 29;16:170. doi: 10.1186/s12885-016-2209-1.

Clinical application of genomic profiling to find druggable targets for adolescent and young adult (AYA) cancer patients with metastasis.

Cha S1, Lee J2, Shin JY3, Kim JY4, Sim SH5, Keam B6,7, Kim TM8,9, Kim DW10,11, Heo DS12,13, Lee SH14,15,16,17, Kim JI18,19,20,21.

Author information

1
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. soojincha36@gmail.com.
2
Interdisciplinary Program for Bioengineering of Graduate School, Seoul National University, Seoul, Republic of Korea. jeleedict@gmail.com.
3
Genomic Medicine Institute, Seoul National University, Seoul, Republic of Korea. jongyeon.anna@gmail.com.
4
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. medijiyeon@gmail.com.
5
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. cantusprote@gmail.com.
6
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. bhumsuk@snu.ac.kr.
7
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. bhumsuk@snu.ac.kr.
8
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. gabriel9@snu.ac.kr.
9
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. gabriel9@snu.ac.kr.
10
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. kimdw@snu.ac.kr.
11
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. kimdw@snu.ac.kr.
12
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. heo1013@snu.ac.kr.
13
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. heo1013@snu.ac.kr.
14
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. sehoon.lee119@gmail.com.
15
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. sehoon.lee119@gmail.com.
16
Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. sehoon.lee119@gmail.com.
17
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea. sehoon.lee119@gmail.com.
18
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. jongil@snu.ac.kr.
19
Genomic Medicine Institute, Seoul National University, Seoul, Republic of Korea. jongil@snu.ac.kr.
20
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea. jongil@snu.ac.kr.
21
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea. jongil@snu.ac.kr.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
26925973
PMCID:
PMC4772349
DOI:
10.1186/s12885-016-2209-1
[Indexed for MEDLINE]
Free PMC Article

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