We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us

Download Mobile App




Germline Genetic Testing Assesses Inherited Risk for Myeloid Malignancies

By LabMedica International staff writers
Posted on 26 Dec 2019
Inherited risk for hematologic malignancies was historically thought to be relatively rare; however, the increased use of next-generation sequencing has identified more patients with germline genetic mutations that are known to increase cancer risk.

Older acute myeloid leukemia (AML) patients are not typically offered germline genetic testing to assess their inherited risk for myeloid malignancies. More...
When cancer risk mutations are identified in patients with hematologic malignancies, this knowledge can inform treatment, and help determine whether family members, who may or may not have inherited the same mutation, can be donors for stem cell transplantation.

Scientists at Foundation Medicine (Cambridge, MA, USA) and their colleagues analyzed 179 AML participants who provided tumor samples from bone marrow or blood, and normal samples from saliva or skin for genetic analysis. Tumor and normal samples were analyzed by Foundation Medicine using its FoundationOne Heme next-generation sequencing test, and the normal samples were analyzed by Oregon Health & Science University (OHSU, Portland, OR, USA) on its GeneTrails hematological malignancies NGS panel.

The results of the tests conducted independently by the two laboratories yielded a 14% prevalence of germline pathogenic variants, or 27 mutations in 24 AML patients. The teams classified 181 variants of unknown significance in 102 patients, a prevalence of 57%. There were seven variant calls that were discordant between the two groups and were excluded because a consensus determination could not be reached.

DDX41 mutations, which have been previously described in older AML patients, were identified in five patients and were the most commonly identified pathogenic germline risk marker in the study. Mutations were also identified in CHEK2, SBDS, MPL, BRCA2, and the Fanconi anemia-associated genes FANCA and FANCL, among others. However, the vast majority of mutations identified in the analysis were variants of uncertain significance (VUS), and the most common were VUS in DOCK8 and CREBBP with a prevalence of more than 5%.

The investigators compared the median variant allele frequency of somatic mutations in skin and saliva samples from 37 patients, and found that the variant allele frequency was significantly lower in the former (8% versus 20%). They determined, as other groups have, that saliva may not be a good option when collecting "matched" normal samples from patients at the time of AML diagnosis.

Uma Borate, MD, MS, an Oncologist and senior author of the study, said, “If we suspect an inherited predisposition to AML, we really want to be careful about the donors we're using, particularly if they're family members. The risk is the donors could have the same mutation and pass that on to the patient in these stem cells and that those stem cells may go on to develop the same malignancy.” The study was presented at the American Society of Hematology annual meeting held December 7-10, 2019 in Orlando, FL, USA.

Related Links:
Foundation Medicine
Oregon Health & Science University



New
Gold Member
Automatic Hematology Analyzer
DH-800 Series
Portable Electronic Pipette
Mini 96
HBV DNA Test
GENERIC HBV VIRAL LOAD VER 2.0
Gold Member
Hematology Analyzer
Medonic M32B
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Immunology

view channel
Image: The CloneSeq-SV approach can allow researchers to study how cells within high-grade serous ovarian cancer change over time (Photo courtesy of MSK)

Blood Test Tracks Treatment Resistance in High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) is often diagnosed at an advanced stage because it spreads microscopically throughout the abdomen, and although initial surgery and chemotherapy can work, most... Read more

Industry

view channel
Image: The collaboration aims to improve access to Hb variant testing with the Gazelle POC diagnostic platform (Photo courtesy of Hemex Health)

Terumo BCT and Hemex Health Collaborate to Improve Access to Testing for Hemoglobin Disorders

Millions of people worldwide living with sickle cell disease and other hemoglobin disorders experience delayed diagnosis and limited access to effective care, particularly in regions where testing is scarce.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.