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Rapid detection of germline mutations for hereditary gastrointestinal polyposis/cancers using HaloPlex target enrichment and high-throughput sequencing technologies
- Source :
- Familial Cancer. 15:553-562
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Genetic testing for hereditary colorectal polyposis/cancers has become increasingly important. Therefore, the development of a timesaving diagnostic platform is indispensable for clinical practice. We designed and validated target enrichment sequencing for 20 genes implicated in familial gastrointestinal polyposis/cancers in 32 cases with previously confirmed mutations using the HaloPlex enrichment system and MiSeq. We demonstrated that HaloPlex captured the targeted regions with a high efficiency (99.66 % for covered target regions, and 99.998 % for breadth of coverage), and MiSeq achieved a high sequencing accuracy (98.6 % for the concordant rate with SNP arrays). Using this approach, we correctly identified 33/33 (100 %) confirmed alterations including SNV, small INDELs and large deletions, and insertions in APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, PMS2, and SKT11. Our approach yielded the sequences of 20 target genes in a single experiment, and correctly identified all previously known mutations. Our results indicate that our approach successfully detected a wide range of genetic variations in a short turnaround time and with a small sample size for the rapid screening of known causative gene mutations of inherited colon cancer, such as familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, and Juvenile polyposis syndrome.
- Subjects :
- 0301 basic medicine
Cancer Research
DNA Mutational Analysis
Peutz-Jeghers Syndrome
Colorectal polyposis
Biology
MLH1
Familial adenomatous polyposis
03 medical and health sciences
0302 clinical medicine
Germline mutation
Neoplastic Syndromes, Hereditary
Gene Duplication
Genetics
medicine
Humans
Juvenile polyposis syndrome
Germ-Line Mutation
Genetics (clinical)
Gastrointestinal Neoplasms
Sequence Deletion
Genetic testing
medicine.diagnostic_test
Intestinal Polyposis
High-Throughput Nucleotide Sequencing
Reproducibility of Results
medicine.disease
Colorectal Neoplasms, Hereditary Nonpolyposis
BMPR1A
Lynch syndrome
030104 developmental biology
Adenomatous Polyposis Coli
Oncology
030220 oncology & carcinogenesis
Subjects
Details
- ISSN :
- 15737292 and 13899600
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Familial Cancer
- Accession number :
- edsair.doi.dedup.....afb45af6b08ed88d266dfa77c407fcfc