Efficient identification of somatic mutations in acute myeloid leukaemia using whole exome sequencing of fingernail derived DNA as germline control

Abstract

Recent advances in next-generation sequencing have made it possible to perform genome wide identification of somatic mutation in cancers. Most studies focus on identifying somatic mutations in the protein coding portion of the genome using whole exome sequencing (WES). Every human genome has around 4 million single nucleotide polymorphisms (SNPs). A sizeable fraction of these germline SNPs is very rare and will not be found in the databases. Thus, in order to unambiguously identify somatic mutation, it is absolutely necessary to know the germline SNPs of the patient. While a blood sample can serve as source of germline DNA from patients with solid tumours, obtaining germline DNA from patients with haematological malignancies is very difficult. Tumor cells often infiltrate the skin, and their DNA can be found in saliva and buccal swab samples. The DNA in the tips of nails stems from keratinocytes that have undergone keratinization several months ago. DNA was successfully extracted from nail clippings of 5 probands for WES. We were able to identify somatic mutations in one tumor exome by using the nail exome as germline reference. Our results demonstrate that nail DNA is a reliable source of germline DNA in the setting of hematological malignancies.

Universal germline genetic testing in patients with hematologic malignancies using DNA isolated from nail clippings

“…Nail clippings represent a non-invasive source of DNA that can be used for germline testing 7,8 . Here, we describe a novel, clinically validated, and New York State Department of Health approved next generation sequencing assay for germline testing of patients with HM using DNA isolated from nail clippings.…”

Applications of probability and statistics in cancer genomics

“…Further, blood from solid tumor patients might contain circulating tumor cells [33], especially in patients with metastatic tumors, rendering this option also sub-optimal. Nail biopsy has been proposed recently as a highly promising normal control although its clinical utility remains to be established [34]. Clearly, detection power can be severely compromised in a tumor-normal matched sequencing design when the tumor-in-normal contamination level is substantial (Fig.…”

Pedigree Investigation, Clinical Characteristics and Prognosis Analysis of Hematological Disease Patients with Germline TET2 Mutation

“…We collected bone marrow (BM) or peripheral blood (PB) as somatic DNA origin, and nails or hairs as germline DNA origin (1,4,23). All patients offered both the BM/PB sample and nails/hairs to carried out somatic and germline TET2 mutation tests, respectively.…”