TY - JOUR
T1 - Improving the detection of patients with inherited predispositions to hematologic malignancies using next-generation sequencing-based leukemia prognostication panels
AU - DiNardo, Courtney D.
AU - Routbort, Mark J.
AU - Bannon, Sarah A.
AU - Benton, Christopher Brent
AU - Takahashi, Koichi
AU - Kornblau, Steve M.
AU - Luthra, Rajyalakshmi
AU - Kanagal-Shamanna, Rashmi
AU - Medeiros, L. Jeffrey
AU - Garcia-Manero, Guillermo
AU - M. Kantarjian, Hagop
AU - Futreal, P. Andrew
AU - Meric-Bernstam, Funda
AU - Patel, Keyur P.
N1 - Funding Information:
This work was supported in part by The University of Texas MD Anderson Cancer Center Support Grant (CA016672), the Charif Souki Cancer Research Fund, The University of Texas MD Anderson Cancer Center Leukemia Specialized Program of Research Excellence (SPORE grant P50 CA100632), and generous philanthropic contributions to MD Anderson’s MDS/AML Moon Shot Program.
Publisher Copyright:
© 2018 American Cancer Society
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Recognizing and referring patients with possible inherited cancer predisposition syndromes for appropriate genetic evaluation and testing provides insights into optimal patient treatment approaches and also can provide education and testing opportunities for family members. Next-generation sequencing (NGS)-based, targeted genotyping for somatic mutations is increasingly used in the diagnosis, prognostication, and treatment selection for patients with hematologic malignancies. However, certain mutations that may be somatically acquired can also be present as germline mutations in some individuals and families. Whether the results of NGS-based leukemia panels can be used to inform decisions and subsequent evaluation of patients with possible inherited cancer predispositions has not been described previously. Because a normal control often is not available when using NGS panels in patients with hematologic malignancies, NGS panel results offer both an opportunity and a challenge to determine the origin and pathogenicity of identified mutations. In the absence of a matched germline control, variant allele frequency (VAF) estimation and data from publically available data sets provide important clues to the possible germline origin of a variant. Careful annotation and review of NGS panels in patients with hematologic malignancies can provide a useful screening tool to systematically improve upon the detection of potentially pathogenic germline variants. Cancer 2018;124:2704-2713.
AB - Recognizing and referring patients with possible inherited cancer predisposition syndromes for appropriate genetic evaluation and testing provides insights into optimal patient treatment approaches and also can provide education and testing opportunities for family members. Next-generation sequencing (NGS)-based, targeted genotyping for somatic mutations is increasingly used in the diagnosis, prognostication, and treatment selection for patients with hematologic malignancies. However, certain mutations that may be somatically acquired can also be present as germline mutations in some individuals and families. Whether the results of NGS-based leukemia panels can be used to inform decisions and subsequent evaluation of patients with possible inherited cancer predispositions has not been described previously. Because a normal control often is not available when using NGS panels in patients with hematologic malignancies, NGS panel results offer both an opportunity and a challenge to determine the origin and pathogenicity of identified mutations. In the absence of a matched germline control, variant allele frequency (VAF) estimation and data from publically available data sets provide important clues to the possible germline origin of a variant. Careful annotation and review of NGS panels in patients with hematologic malignancies can provide a useful screening tool to systematically improve upon the detection of potentially pathogenic germline variants. Cancer 2018;124:2704-2713.
KW - gene panel
KW - germline
KW - inherited
KW - mutation
KW - next-generation sequencing (NGS)
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U2 - 10.1002/cncr.31331
DO - 10.1002/cncr.31331
M3 - Review article
C2 - 29682723
AN - SCOPUS:85048627422
SN - 0008-543X
VL - 124
SP - 2704
EP - 2713
JO - Cancer
JF - Cancer
IS - 13
ER -