Cell-free DNA from nail clippings as source of normal control for genomic studies in hematologic malignancies

作者：Melissa Krystel‐Whittemore, Kseniya Petrova‐Drus, Ryan Ptashkin, Mark D. Ewalt, JinJuan Yao, Ying Liu, Menglei Zhu, Jamal Benhamida, Benjamin H. Durham, Jyoti Kumar, Khédoudja Nafa, Iwona Kiecka, Anita S. Bowman, Erika Gedvilaite, Jacklyn Casanova, Yun-Te Lin, Abhinita Mohanty, Satshil Rana, Anoop Balakrishnan Rema, Ivelise Rijo, Nelio Chaves, Paulo Salazar, Anita Yun, Sean Lachhander, Wei Wang, Mohammad Shamsul Haque, Wenbin Xiao, Mikhail Roshal, Sergio Giralt, Gilles Salles, Raajit K. Rampal, Eytan M. Stein, Miguel‐Angel Perales, Steven M. Horwitz, Ann A. Jakubowski, Doris M. Ponce, Alina Markova, Ozge Ceyhan‐Birsoy, Diana Mandelker, Simon Mantha, Ahmet Doǧan, Ryma Benayed, Marc Ladanyi, Michael F. Berger, A. Rose Brannon, Ahmet Zehir, Chad Vanderbilt, Maria E. Arcila · 发表于：Haematologica · 年份：2024 · DOI：10.3324/haematol.2024.285054 · 被引用次数：9 · 研究领域：Cancer Genomics and Diagnostics、Lymphoma Diagnosis and Treatment、Chronic Myeloid Leukemia Treatments

Comprehensive genomic sequencing is becoming a critical component in the assessment of hematologic malignancies, with broad implications for patients' management. In this context, unequivocally discriminating somatic from germline events is challenging but greatly facilitated by matched analysis of tumor:normal pairs of samples. In contrast to solid tumors, in hematologic malignancies conventional sources of normal control material (peripheral blood, buccal swabs, saliva) could be highly involved by the neoplastic process, rendering them unsuitable. In this work we describe our real-world experience using cell-free DNA (cfDNA) isolated from nail clippings as an alternate source of normal control material, through the dedicated review of 2,610 tumor:nail pairs comprehensively sequenced by MSK-IMPACT-heme. Overall, we found that nail cfDNA is a robust germline control for paired genomic studies. In a subset of patients, nail DNA may be contaminated by tumor DNA, reflecting unique attributes of the hematologic disease and transplant history. Contamination is generally low level, but significantly more common among patients with myeloid neoplasms (20.5%; 304/1,482) than among those with lymphoid diseases (5.4%; 61/1,128) and particularly enriched in myeloproliferative neoplasms with marked myelofibrosis. When identified in patients with lymphoid and plasma-cell neoplasms, mutations commonly reflected a myeloid profile and correlated with a concurrent/evolving clonal myeloid neopl...