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Last update 08 May 2025

N.N. Petrov National Medical Research Center of Oncology

Russia|

www.niioncologii.ru

Russia|

www.niioncologii.ru

Last update 08 May 2025

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Translational Medicine

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100 Clinical Results associated with N.N. Petrov National Medical Research Center of Oncology

0 Patents (Medical) associated with N.N. Petrov National Medical Research Center of Oncology

111

Literatures (Medical) associated with N.N. Petrov National Medical Research Center of Oncology

21 Apr 2025·Cancer Research

Abstract 1491: ATM, CHEK2 and BLM mutant prostate cancers do not have high homologous recombination deficiency scores

Author: Kuligina, Ekaterina Sh. ; Otradnova, Ekaterina A. ; Iyevleva, Aglaya G. ; Aleksakhina, Svetlana N. ; Imyanitov, Evgeny N. ; Sokolenko, Anna P. ; Syomina, Maria V.

Background:Homologous recombination deficiency (HRD) resulting from inactivating mutations in the BRCA1 and BRCA2 genes promotes increased chromosomal instability and renders tumor cells susceptible to platinum derivatives and PARP inhibitors. Hereditary and/or somatic mutations in BRCA2, ATM, CHEK2 and other loci involved in homologous recombination DNA repair (HRR) have been reported in up to 25% of metastatic prostate cancer (PC) cases. The contribution of alterations in HRR-related genes beyond BRCA1/2 to homologous recombination deficiency remains largely unknown. The aim of the current study was to compare the HRD scores in prostate tumors with alterations in different HRR genes.Methods:HRD scores were determined as the sum of genomic loss of heterozygosity (LOH), large-scale state transition (LST) and telomeric allelic imbalance (TAI) scores by targeted NGS using HiSNP Ultra Panel v1.0 (Nanodigmbio, China) in two PC groups. The first group consisted of 58 PC cases with germline or somatic mutations in any of 34 HRR genes, while the second group included 214 cases without HRR mutations. The cut-off for the presence of homologous recombination deficiency was set as an HRD score ≥ 42.Results:HRD was observed more frequently in PCs with HRR mutations (9/58, 16%) than in cases without detectable HRR alterations (10/214, 5%, p = 0.008). In the HRR-mutated subgroup, high HRD scores were found in cases with BRCA2 (n = 4), ATM (n = 2), CDK12, NBN and FANCM mutations. The median HRD scores in PCs with mutations in BRCA2 (n = 9), ATM (n = 12), CHEK2 (n =8), NBN (n = 3), FANCM (n = 3), BRCA1 (n = 3), BLM (n = 3) were 41, 22.5, 7.5, 3, 10, 6, and 3, respectively. The comparison of HRD scores between BRCA2-mutant cases and ATM- (p = 0.046), CHEK2- (p = 0.005), or BLM-mutant PCs (p = 0.042) reached statistical significance. The presence of somatic TP53 mutations was associated with a higher degree of chromosomal instability and elevated HRD scores (p = 0.0001).Conclusions:A high HRD score is observed in a noticeable proportion of prostate tumors lacking mutations in the HRR genes. Prostate cancer cases with alterations in ATM, CHEK2, BLM, and possibly also NBN, FANCM genes are unlikely to have severe HRD. This work has been supported by the Russian Science Foundation (grant number 23-15-00262).Citation Format:Ekaterina Sh. Kuligina, Aglaya G. Iyevleva, Anna P. Sokolenko, Svetlana N. Aleksakhina, Maria V. Syomina, Ekaterina A. Otradnova, Evgeny N. Imyanitov. ATM, CHEK2 and BLM mutant prostate cancers do not have high homologous recombination deficiency scores [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1491.

01 Apr 2025·Biogerontology

Distinguishing the intrinsic and extrinsic causes of changes in human mortality by examining life-table aging rate (LAR) trajectories through the lens of generalized Gompertz-Makeham law

Article

Author: Golubev, A

To check whether the reported waves of age-dependent changes in multiomics patterns in humans influence age-specific mortality, life-table aging rate (LAR) trajectories derived from Human Morality Database (HMD) data were modeled based on assumptions inherent in a generalized Gompertz-Makeham Law (gGML). The gGML implies that any changes in resistance to causes of death (CoD) and in exposure to CoD are translated into changes in mortality in an exponential and a linear way, respectively. Modeling suggests that undulations of LAR trajectories derived from HMD data on countries where life expectancy (LE) is above 83 years do not align with the reported waves of multiomics changes and are rather associated with changes in the exposure to CoD. As far as the exposure may be modifiable, it may be inferred from modeling that the contribution of the modifiable CoD to the total mortality is almost 100% at 25 years and reaches zero after ca. 90 years, which is no surprise. Unexpectedly, the contribution may increase by 20% at 55-65 years after the initial decrease, which reaches 30 to 70% at about 40 years. Reasons to revise approaches to attributing mortality to different CoD are discussed. Gains in LE possible upon eliminating all modifiable CoD are estimated. In the countries where LE currently exceeds 83 years, the estimates are 2.9-5.7 years for men and 1.2-2.5 for women. Thus, human LE may approach but hardly can ever exceed 90 years.

01 Mar 2025·The Thoracic and Cardiovascular Surgeon

Evaluation of Risk Factors for Early Insufficiency after Bronchial Sleeve Resections

Article

Author: Levchenko, Nikita ; Shabinskaya, Viktoriia ; Levchenko, Evgeny ; Ergnyan, Stepan ; Mamontov, Oleg ; Mikhnin, Alexander

Abstract Background Bronchoplastic resections are now widely used as a surgical treatment for resectable central lung cancer. However, bronchial dehiscence is one of the most life-threatening complications, making it important to identify its risk factors to separate patients who require more attention during the postoperative period. Methods The data of 285 patients who underwent bronchoplasty from 2006 to 2021 were retrospectively reviewed. We collected demographic characteristics, history of neoadjuvant therapy, preoperative assessment, perioperative outcomes, and postoperative complications to investigate different variables as risk factors for bronchial dehiscence by univariate and multivariate analyses. Results Bronchial dehiscence was diagnosed in 12 patients (4.2%) with a mean presentation on postoperative day 10 (range: 1–24 days). By multivariate analysis, current smoking (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.1–20.1, p = 0.032), chronic obstructive pulmonary disease (COPD; OR: 6.5, 95% CI: 1.2–33.8, p = 0.027), bronchoplastic right lower lobectomy (OR: 12.9, 95% CI: 2.4–69.7, p = 0.003), and upper sleeve bilobectomy with segmentectomy S6 by performing an anastomosis between right main bronchus (RMB) and bronchus of basal pyramid (BP) (OR: 30.4, 95% CI: 3.4–268.1, p = 0.002) were confirmed as relevant risk factors for developing bronchial dehiscence. Conclusion Current smoking, COPD, bronchoplastic right lower lobe, and upper l with segmentectomy S6 by performing an anastomosis between RMB and bronchus of BP were identified with the occurrence of bronchial dehiscence after sleeve resection.

100 Deals associated with N.N. Petrov National Medical Research Center of Oncology

100 Translational Medicine associated with N.N. Petrov National Medical Research Center of Oncology

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