Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/130867
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Targeted gene panels identify a high frequency of pathogenic germline variants in patients diagnosed with a hematological malignancy and at least one other independent cancer |
Author: | Singhal, D. Hahn, C.N. Feurstein, S. Wee, L.Y.A. Moma, L. Kutyna, M.M. Chhetri, R. Eshraghi, L. Schreiber, A.W. Feng, J. Wang, P.P.-S. Babic, M. Parker, W.T. Gao, S. Moore, S. Das, S. Thomas, D. Pattnaik, S. Brown, A.L. D'Andrea, R.J. et al. |
Citation: | Leukemia, 2021; 35(11):3245-3256 |
Publisher: | Springer |
Issue Date: | 2021 |
ISSN: | 0887-6924 1476-5551 |
Statement of Responsibility: | Deepak Singhal, Christopher N. Hahn, Simone Feurstein, Li Yan A. Wee, Luke Moma, Monika M. Kutyna ... et al. |
Abstract: | The majority of studies assessing the contribution of pathogenic germline variants (PGVs) to cancer predisposition have focused on patients with single cancers. We analyzed 45 known cancer predisposition genes (CPGs) in germline samples of 202 patients with hematological malignancies (HMs) plus one or more other independent cancer managed at major tertiary medical centers on two different continents. This included 120 patients with therapy-related myeloid neoplasms (t-MNs), where the HM occurred after cytotoxic treatment for a first malignancy, and 82 patients with multiple cancers in which the HM was not preceded by cytotoxic therapy (MC-HM). Using American College of Medical Genetics/Association for Molecular Pathology variant classification guidelines, 13% of patients had PGVs, most frequently identified in CHEK2 (17% of PGVs), BRCA1 (13%), DDX41 (13%), and TP53 (7%). The frequency of PGVs in MC-HM was higher than in t-MN, although not statistically significant (18 vs. 9%; p = 0.085). The frequency of PGVs in lymphoid and myeloid HM patients was similar (19 vs. 17.5%; p > 0.9). Critically, patients with PGVs in BRCA1, BRCA2 or TP53 did not satisfy current clinical phenotypic criteria for germline testing. Our data suggest that a personal history of multiple cancers, one being a HM, should trigger screening for PGVs. |
Keywords: | Humans Neoplasms Hematologic Neoplasms Genetic Predisposition to Disease BRCA1 Protein BRCA2 Protein Prognosis Retrospective Studies Follow-Up Studies Germ-Line Mutation Adolescent Adult Aged Aged, 80 and over Middle Aged United States Female Male Tumor Suppressor Protein p53 Young Adult Biomarkers, Tumor |
Description: | Published online: 13 April 2021 |
Rights: | © Crown 2021. |
DOI: | 10.1038/s41375-021-01246-w |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1164601 http://purl.org/au-research/grants/nhmrc/1024215 http://purl.org/au-research/grants/nhmrc/1195517 |
Published version: | http://dx.doi.org/10.1038/s41375-021-01246-w |
Appears in Collections: | Aurora harvest 8 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.