821P - Circulating chromosomal alterations in lymphoid malignancies

Background

Mosaic chromosomal alterations (mCAs) are a promising biomarker for lymphoid malignancies (LMs). mCAs represent a form of clonal hematopoiesis, characterized by mega-base-scale loss, copy-neutral loss of heterozygosity (CN-LOH), and gain events. Prior studies have found mCAs in regions associated with lymphoid malignancies conferred 11-fold increased risk of developing a LM overall. However, mCAs associated with each LM subtype have not been examined at scale and refined characterization of mCAs is needed.

Methods

We analyzed mCAs in our case-control study of 3,246 LM cases and 1,006 controls (Table). mCAs were called using the MoChA algorithm on SNP-array genotyping of DNA from peripheral blood. mCAs detected in >1% of cells and with >1Mb length were examined. We compared mCA frequency, type (i.e., loss, CN-LOH, gain), location, cell fraction (i.e., proportion of cells with the mCA), and length. Logistic regression was used to test for association of mCA prevalence with each major LM subtype, adjusting for age and sex.

Results

Compared to individuals without a prior cancer, mCAs were significantly more common among individuals with any LM (odds ratio, OR = 7.2; 95% confidence interval, CI: 5.3-9.9; Table). The prevalence of mCAs differed by LM subtype, ranging from 7% to 74%. mCAs were significantly enriched in each subtype of LM, however the strength of the association ranged from 1.7-fold (multiple myeloma, MM) to 62.8-fold (chronic lymphocytic leukemia, CLL). Some mCAs were shared across some LM subtypes but not others, e.g., loss of 13q was the most common event in MM, CLL, and mantel cell lymphoma, but was rarely observed in marginal zone, follicular (FL), and diffuse large B-cell lymphoma (DLBCL). Other mCAs appear to be specific to one LM subtype, e.g., CN-LOH of 1q was mainly observed in DLBCL and gain of 18 in FL. Table: 821P

Frequency of autosomal mCAs by lymphoid malignancy subtype

Conclusions

This largest study of mCAs in individuals with an LM supports that specific mCA events play a role certain subtypes. Ultimately, these findings may lead to more precise biomarkers for LM risk.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.