RESUMO
Background@#Structural variants (SVs) are currently analyzed using a combination of conventional methods; however, this approach has limitations. Optical genome mapping (OGM), an emerging technology for detecting SVs using a single-molecule strategy, has the potential to replace conventional methods. We compared OGM with conventional diagnostic methods for detecting SVs in various hematologic malignancies. @*Methods@#Residual bone marrow aspirates from 27 patients with hematologic malignancies in whom SVs were observed using conventional methods (chromosomal banding analysis, FISH, an RNA fusion panel, and reverse transcription PCR) were analyzed using OGM. The concordance between the OGM and conventional method results was evaluated. @*Results@#OGM showed concordance in 63% (17/27) and partial concordance in 37% (10/27) of samples. OGM detected 76% (52/68) of the total SVs correctly (concordance rate for each type of SVs: aneuploidies, 83% [15/18]; balanced translocation, 80% [12/15] unbalanced translocation, 54% [7/13] deletions, 81% [13/16]; duplications, 100% [2/2] inversion 100% [1/1]; insertion, 100% [1/1]; marker chromosome, 0% [0/1];isochromosome, 100% [1/1]). Sixteen discordant results were attributed to the involvement of centromeric/telomeric regions, detection sensitivity, and a low mapping rate and coverage. OGM identified additional SVs, including submicroscopic SVs and novel fusions, in five cases. @*Conclusions@#OGM shows a high level of concordance with conventional diagnostic methods for the detection of SVs and can identify novel variants, suggesting its potential utility in enabling more comprehensive SV analysis in routine diagnostics of hematologic malignancies, although further studies and improvements are required.
RESUMO
Background@#The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis. @*Methods@#Participants with AVS (valves ≥ 2 mm thick, high echogenicity, and a peak trans-aortic velocity of < 2.5 m/sec) and an age- and sex-matched control group were enrolled.Twenty-four CHIP genes with common variants in cardiovascular disease were used to generate a next-generation sequencing panel. The primary endpoint was the CHIP detection rate between the AVS and control groups. Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for differences in baseline characteristics. @*Results@#From April 2020 to April 2022, 187 participants (125 with AVS and 62 controls) were enrolled; the mean age was 72.6 ± 8.5 yrs, and 54.5% were male. An average of 1.3CHIP variants was observed. CHIP detection, defined by a variant allele frequency (VAF) of≥ 0.5%, was similar between the groups. However, the AVS group had larger CHIP clones:49 (39.2%) participants had a VAF of ≥ 1% (vs. 13 [21.0%] in the control group; P = 0.020), and 25 (20.0%) had a VAF of ≥ 2% (vs. 4 [6.5%]; P = 0.028). AVS is independently associated with a VAF of ≥ 1% (adjusted odds ratio: 2.44, 95% confidence interval: 1.11–5.36; P = 0.027). This trend was concordant and clearer in the IPTW cohort. @*Conclusions@#Participants with AVS more commonly had larger CHIP clones than age- and sex-matched controls. Further studies are warranted to identify causality between AVS and CHIP.