Expression Levels of NOTCH3 Minus Exon 16 as a Potential Prognostic Biomarker in Diffuse Large B-Cell Lymphoma

Share this content:
Spliced events in NOTCH genes may facilitate risk stratification for patients with certain subtypes of DLBCL.
Spliced events in NOTCH genes may facilitate risk stratification for patients with certain subtypes of DLBCL.

Low transcript expression levels of a specific NOTCH3 splice variant, NOTCH3 excluding exon 16 (NOTCH3 – exon 16), show potential as a negative prognostic biomarker that may also be predictive of vincristine resistance in patients classified as having germinal center B cell (GCB) diffuse large B-cell lymphoma (DLBCL), according to a study published in Scientific Reports

The heterogeneous nature of DLBCL, characterized by diverse clinical presentations, cellular morphological and molecular characteristics, response to chemotherapy, and survival outcomes, has led to the development of a number of DLBCL classification systems. In order to enhance risk stratification of patients with DLBCL, researchers investigated whether alternative events in mRNA splicing and exon usage could serve as potential biomarkers. Previous molecular studies of the role of NOTCH genes as drivers of hematological malignancies have typically been focused at the DNA level. 

A retrospective analysis determined baseline characteristics and disease subtype classifications of 75 patients with DLBCL. Alternatively spliced genes were identified in 37 DLBCL specimens. Loss of exon 16 in NOTCH3 transcripts was observed for the GCB-centroblast subtype, but not the GCB-centrocyte subtype.  Interestingly, DNA analyses of NOTCH3 did not distinguish the GCB-centroblast and GCB-centrocyte subtypes. In addition, higher expression levels of the NOTCH3 – exon 16 transcript were associated with higher sensitivity to vincristine in GCB-classified patients. While expression levels of NOTCH3 – exon 16 transcripts were not demonstrated to have independent prognostic significance in DLBCL, a trend for association of overall survival for R-CHOP treated patients and NOTCH3 – exon 16 expression level was observed within the GCB subclass (P =.07). 

“This pilot study indicates that altered alternative splicing contributes to the pathogenesis of DLBCL depending on the molecular subtypes and may be promising as prognostic and predictive biomarkers,” the authors concluded. “More studies using a larger independent patient cohort are required to confirm the impact of the NOTCH3 – exon 16 transcript on overall survival of GCB DLBCL patients.”

Reference

  1. Jespersen DS, Schönherz AA, Due H, Bøgsted M, Sondergaard TE, Dybkær K. Expression of NOTCH3 exon 16 differentiates Diffuse Large B-cell Lymphoma into molecular subtypes and is associated with prognosis. Sci Rep. 2019;9(1):335. doi: 10.1038/s41598-018-36680-x

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters



Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs