Patients with diffuse large B-cell lymphoma (DLBCL) may have mutational differences between biopsy sites, according to a study published in Leukemia & Lymphoma.
During the study, half of the patients with DLBCL (8 out of 16) had mutational differences, including differences in TP53 mutational status, between 2 spatially distinct biopsy sites. These findings could have implications for the selection of biopsy sites and treatment decisions.
Of the 8 patients with mutational differences between biopsy sites, 6 had a single additional mutation in 1 biopsy (Group A) while the other 2 patients had more significant differences between the biopsies (Group B). In 5 of the 6 patients in Group A, the additional mutation was found in the extranodal biopsy, and the mutation was in TP53 in 2 of the patients’ extranodal sites.
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Both of the group B patients underwent a nodal and extranodal biopsy. In 1 patient, the mutational profiles were completely different between the 2 sites. The other patient had MYD88 hotspot mutations at both sites but several different PIM1 mutations, and 1 site had an FBXW7 mutation.
“We found potentially clinically relevant mutational differences in 50% of the patients, including additional TP53 mutations in extranodal biopsies. Our findings challenge the use of a single biopsy mutational status for treatment decisions and patient stratification in clinical trials,” the authors wrote.
Since the majority of the additional mutations were located in extranodal sites, especially the TP53 mutations, the authors suggested that these sites be prioritized in biopsy collection as they contain the more advanced clone in most cases.
The average age of the patients was 71.8 years, and the majority had stage IV disease at the time of diagnosis/project inclusion. The patients in the study had de novo DLBCL, and the biopsies were collected prior to treatment. Five patients had both biopsies collected from nodal sites, 3 patients had both biopsies taken from extranodal sites, and 8 patients had paired nodal/extranodal sites of collection.
Hersby DS, Schejbel L, Breinholt MF, et al. Multi-site pre-therapeutic biopsies demonstrate genetic heterogeneity in patients with newly diagnosed diffuse large B-cell lymphoma. Leuk Lymphoma. Published online June 16, 2023. doi:10.1080/10428194.2023.2220454