Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma

Abstract

Fluorescence in situ hybridization (FISH) is currently the gold-standard assay to detect recurrent genomic abnormalities of prognostic significance in multiple myeloma (MM). Since most translocations in MM involve a position effect with heterogeneous breakpoints, we hypothesize that FISH has the potential to miss translocations involving these regions. We evaluated 70 bone marrow samples from patients with plasma cell dyscrasia by FISH and whole-genome mate-pair sequencing (MPseq). Thirty cases (42.9%) displayed at least one instance of discordance between FISH and MPseq for each primary and secondary abnormality evaluated. Nine cases had abnormalities detected by FISH that went undetected by MPseq including 6 tetraploid clones and three cases with missed copy number abnormalities. In contrast, 19 cases had abnormalities detected by MPseq that went undetected by FISH. Seventeen were MYC rearrangements and two were 17p deletions. MPseq identified 36 MYC abnormalities and 17 (50.0% of MYC abnormal group with FISH results) displayed a false negative FISH result. MPseq identified 10 cases (14.3%) with IgL rearrangements, a recent marker of poor outcome, and 10% with abnormalities in genes associated with lenalidomide response or resistance. In summary, MPseq was superior in the characterization of rearrangement complexity and identification of secondary abnormalities demonstrating increased clinical value compared to FISH.

Development and Validation of a Prognostic Implications of Chromosome Abnormalities Algorithm for Newly Diagnosed Multiple Myeloma

“…In the multivariate analysis, t (11,14), t (4,14) was not independent prognostic factors of MM patients (p>0.05) no matter the analysis was based on the EMN criteria or based on the cut-off value calculated by Kaps. T (4,14) was considered as a prognostic factor in previous studies (21,22), while bortezomib seemed to improve its adverse effects (23)(24)(25). In this study, among the patients with t(4,14) ≥10%, the treatment contains bortezomib accounted for 89.36%.…”

“…The results presented that patients harbored 17p-, 13q-, 1q21+ showed shorter OS and patients harbored 17p-, 1q21+ have shorter PFS based on the EMN criteria. Then, we used Kaps to calculate the best cut-off value of OS and the results showed that the best cut-off value of OS were as follows: 17p -20.1%, 13q -85%, 1q21 + 39%, t (11,14) 55.5%, t (14,16) 87%, t (4,14) 53.5%. Based on the cut-off value calculated by Kaps, we also found that patients harbored 17p-, 13q-, 1q21+, t(4;14 , t(11;14 , t(14;16 showed shorter OS and patients harbored 17p-, 13q-, 1q21+, t(11;14 , t(14;16 have shorter PFS ( Figure 1).…”

“…In this study, among the patients with t(4,14) ≥10%, the treatment contains bortezomib accounted for 89.36%. It seemed that the survival improvement of patients with t (4,14) may be due to the higher use ratio of bortezomib. As an another adverse prognostic factor, t (14,16) was not the prognostic factor of MM patients when univariate and multivariate analysis according to the cut-off value calculated by Kaps (26).…”

“…The effect of 13q-on prognosis was highly controversial. Some studies suggest that 13q-may lead to poor prognosis (33), while other studies suggested that 13q-alone does not worsen the prognosis of MM patients, but 13q-was associated with prognostic factors 17p-and t (4,14) which leads to poor prognosis (15,34). In this study, we rst performed a survival analysis of patients according to the EMN criteria and we found that although there was a statistical difference between OS in 13q-positive and 13qnegative patients in the univariate analysis.…”

CircMUC16 promotes autophagy of epithelial ovarian cancer via interaction with ATG13 and miR-199a

“…Cell nuclei were stained with Hoechst 33342. Finally, images were obtained on a confocal microscope [15,16]. All experiments were repeated three times.…”