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Figure 2: Mutation type and mutation predictive effect
on gene function changes in all mutations (A, B), CREBBP mutations (C, D), TP53 mutations (E, F), and EHZ2 mutations (G, H).
"Our analysis showed that the presence of CREBBP mutations in tumor biopsies of newly diagnosed GCB DLBCL/HGBL patients was associated with
poorer DFS (disease-free survival) after first-line immunochemotherapy treatment.
"
Buffalo, NY – November 17, 2022 – A new research paper was published November 17, 2022 in Oncotarget's Volume 13 titled "Mutational Analysis of Tumor Biopsy in Patients with Newly Diagnosed Germinal Center Aggressive B-cell Lymphoma.
"
Comprehensive genomic analysis of tumor biopsy tissue from patients with newly diagnosed germinal center B cells (GCB) diffuse large B-cell/high-grade B-cell lymphoma (DLBCL/HGBL) revealed a molecular subtype with a lower predicted survival rate, characterized by somatic mutations
that can be detected by clinical laboratory mutation analysis (CLMA).
To determine the frequency and predictive value of individual genetic mutations associated with the low-risk subgroups defined by these experiments, researchers Daniel J.
Landsburg, Jennifer J.
D.
Morrissette, Stephen J.
Schuster, Sunita D.
Nasta, James N.
Gerson, Stefan K.
Barta, Jakub Svoboda, Elise A.
Chong, And Megan S.
Lin's researchers from the University of Pennsylvania reviewed the results of CLMA treatment for tumors in newly diagnosed GCB DLBCL/HGBL patients who had previously been treated
at the University of Pennsylvania.
"Therefore, we sought to analyze the results of CLMA performed by our institution on tumors in newly diagnosed GCB DLBCL/HGBL patients who had previously received first-line immunochemotherapy to determine the frequency and predictive value
of the presence of individual genetic mutations associated with the low-risk subgroups defined by these experiments.
"
CLMA was successfully performed in 58/59 patients with tumor biopsy, with a median transition period of 16 days, and 51 patients who were routinely undergone with CLMA and had adequate clinical follow-up were analyzed
.
Patients with tumors showing CREBBP mutations had a lower estimated 2-year disease-free survival (DFS) compared with those without a CREBBP mutation (45% [95% CI 18-68%] vs.
67% [95% CI 44-83%], P = 0.
045).
The researchers note that CREBBP mutations may occur frequently and predict inferior DFS
in newly diagnosed GCB DLBCL/HGBL patients.
In addition, CLMA can be practically applied to translate experimental results into results that are more directly applied to risk stratification and clinical trial design for subpopulations of DLBCL/HGBL patients
.
"In summary, CLMA on tumor biopsies of newly diagnosed GCB DLBCL/HGBL patients revealed frequent mutations in CREBBP, which were expected to result in loss of function, as well as a significant reduction
in estimated DFS rates after 2 years.
"
