Conflict of interest: Nothing to report.
Whole exome sequencing of pediatric gastric adenocarcinoma reveals an atypical presentation of Li-Fraumeni syndrome†
Article first published online: 26 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 60, Issue 4, pages 570–574, April 2013
How to Cite
Chang, V. Y., Federman, N., Martinez-Agosto, J., Tatishchev, S. F. and Nelson, S. F. (2013), Whole exome sequencing of pediatric gastric adenocarcinoma reveals an atypical presentation of Li-Fraumeni syndrome. Pediatr. Blood Cancer, 60: 570–574. doi: 10.1002/pbc.24316
- Issue published online: 13 FEB 2013
- Article first published online: 26 SEP 2012
- Manuscript Accepted: 14 AUG 2012
- Manuscript Received: 27 MAY 2012
- St. Baldrick's Foundation Career Development Award
- T32 Developmental Hematology Grant. Grant Number: T32HL086345
- K12 Child Health Research Career Development Award. Grant Number: 2K12HD034610-16
- American Society of Hematology
- exome sequencing;
- Li-Fraumeni Syndrome;
- pediatric gastric adenocarcinoma
Gastric adenocarcinoma is a rare diagnosis in childhood. A 14-year-old male patient presented with metastatic gastric adenocarcinoma, and a strong family history of colon cancer. Clinical sequencing of CDH1 and APC were negative. Whole exome sequencing was therefore applied to capture the majority of protein-coding regions for the identification of single-nucleotide variants, small insertion/deletions, and copy number abnormalities in the patient's germline as well as primary tumor.
Materials and Methods
DNA was extracted from the patient's blood, primary tumor, and the unaffected mother's blood. DNA libraries were constructed and sequenced on Illumina HiSeq2000. Data were post-processed using Picard and Samtools, then analyzed with the Genome Analysis Toolkit. Variants were annotated using an in-house Ensembl-based program. Copy number was assessed using ExomeCNV.
Each sample was sequenced to a mean depth of coverage of greater than 120×. A rare non-synonymous coding single-nucleotide variant (SNV) in TP53 was identified in the germline. There were 10 somatic cancer protein-damaging variants that were not observed in the unaffected mother genome. ExomeCNV comparing tumor to the patient's germline, identified abnormal copy number, spanning 6,946 genes.
We present an unusual case of Li-Fraumeni detected by whole exome sequencing. There were also likely driver somatic mutations in the gastric adenocarcinoma. These results highlight the need for more thorough and broad scale germline and cancer analyses to accurately inform patients of inherited risk to cancer and to identify somatic mutations. Pediatr Blood Cancer 2013; 60: 570–574. © 2012 Wiley Periodicals, Inc.