Search Results (101)

Polemonium L. (Polemoniaceae) is a widespread genus native to subarctic and arctic regions of the Northern Hemisphere. The taxonomy and genome relationships within Polemonium are still unclear. We analyzed genomes of three species from each Polemonium caeruleum and Polemonium pulcherrimum complex using bioinformatic analysis by RepeatExplorer2/TAREAN pipelines of next-generation sequencing data. The repeatomes of all studied species were similar in type and number of repeats. Satellite DNAs (satDNAs) demonstrated high sequence identity within the studied species. FISH chromosome mapping of 45S rDNA, 5S rDNA, and two satDNAs Pol_C 33 and Pol_C 46 allowed us to construct the species karyograms and assess the genome diversity within the P. caeruleum complex and P. pulcherrimum complex, and also confirm the taxonomic status of P. kiushianum as an independent species. Our findings demonstrate a close genomic relationship among the species from P. caeruleum and P. pulcherrimum complexes, indicating the presence of a common ancestral genome; additionally, our results provide cytogenetic evidence for the monophyletic origin of these sections and also complex evolutionary history of the genus Polemonium. The developed approach may be a valuable framework for further investigation of the chromosomal organization of karyotypes in other species of the genus Polemonium. Full article

Homologous recombination deficiency (HRD) resulting from inactivation of BRCA1/2 genes promotes chromosomal instability and renders tumor cells susceptible to platinum derivatives and PARP inhibitors (PARPi). The contribution of alterations in other homologous recombination repair (HRR) genes to HRD remains understudied. This investigation aimed to analyze the spectrum of mutations in 34 HRR genes in prostate carcinomas (PCs) and study the relationship between HRR status and HRD. HRR mutations and HRD scores were examined by NGS in 1131 and 680 PCs, respectively. Pathogenic or likely pathogenic variants in HRR genes were detected in 216/1131 cases (19.1%). HRD, defined by an HRD score cut-off of ≥42, was observed more frequently in HRR-mutated than in wild-type tumors (23/120 (19.2%) vs. 29/560 (5.2%), p < 0.0001). The highest HRD scores were detected in PCs with biallelic inactivation of the BRCA2 or PALB2 genes, as well as in tumors with BRIP1 mutations. HRD was also occasionally seen in PCs with ATM, NBN, FANCM, BRCA1 and CDK12 alterations, but never in cases with CHEK2 mutations. HRD was significantly more associated with aggressive PC features than HRR mutations. The majority of CDK12-mutated tumors exhibited a distinct type of copy number variations (CNV)–a tandem duplication phenotype. Our study suggests that the selection of PC patients for PARPi treatment requires a significant revision of existing attitudes towards tumor genetic profiling. Full article

Birt–Hogg–Dubé (BHD) syndrome is a rare genetic disease, inherited in an autosomal dominant manner, that was first described in the mid-1970s and occurs due to pathogenic variants in the folliculin gene (FLCN) on chromosome 17p11.2. The syndrome has numerous clinical manifestations and primarily affects the lungs, kidneys, and skin. As far as the pulmonary features are concerned, more than 80% of patients appear to develop bilateral pulmonary cysts located in the lower lung zones, in the subpleural area, with cumulative risk of spontaneous pneumothorax depending on the number of cysts in the lungs. Another serious feature of the syndrome is the increased risk of renal cell carcinoma, which is often an incidental finding on screening or medical imaging. Cutaneous manifestations include benign fibrofolliculomas, trichodiscomas, and acrochordons (skin tags), which primarily affect the patients’ emotional status as a result of their cosmetic defects. BHD syndrome is generally an underdiagnosed condition due to the great variability of its clinical picture, thus highlighting the importance of genetic testing for FLCN mutations in suspected cases. The application of ERN GENTURIS guidelines in clinical practice can facilitate early, accurate diagnosis of the disease and optimal personalized management of the patients. Full article

Objectives: This study aimed to determine whether chromosomal mosaicism in blastocysts is associated with a distinct morphokinetic signature. Methods: Preimplantation genetic testing for aneuploidy (PGT-A) was performed on 182 human embryos via trophectoderm biopsy on day 5 and analyzed by next-generation sequencing. Embryos were classified as euploid (n = 55), mosaic (n = 39: 21 low-grade, 18 high-grade), or aneuploid (n = 88), of which 18 with concurrent mosaicism. Prior to biopsy, embryos were cultured in a time-lapse system (EmbryoScope), and 12 morphokinetic parameters were assessed, including pronuclei fading (tPNf), cleavage times (t2–t9), morula formation (tM), blastulation start (tSB), and full blastocyst formation (tB). These parameters were compared according to ploidy status. Results: Patients with euploid and mosaic embryos were comparable in terms of maternal age, ART indication and embryo quality (p > 0.05). In contrast, aneuploid embryos were obtained from older patients and had lower morphological grades. Mosaic embryos showed delayed tPNf (24.8 ± 6.5 vs. 22.8 ± 2.3 h, p = 0.03) and t2 (27.6 ± 6.6 vs. 25.4 ± 2.5 h, p = 0.02) compared to euploid embryos, mainly attributable to low-grade mosaic embryos. Whole-chromosome mosaicism, but not segmental mosaicism, was associated with delayed embryo development at several intermediate cleavage time points (t3, t4, t6, t7 and t9). Aneuploid embryos showed significant delays at later stages versus euploid embryos, particularly aneuploid embryos with mosaicism at t7 (56.6 ± 8.3 vs. 52 ± 5.6 h, p = 0.02), t8 (59.1 ± 9.6 vs. 54.8 ± 6.7 h, p = 0.04), tM (90.3 ± 7.7 vs. 83.6 ± 8.2 h, p = 0.006) and tB (113.0 ± 11.6 vs. 106.6 ± 8.9 h, p = 0.03). Conclusions: Mosaic embryos exhibit delays in early development (tPNf, t2) but reach later morphokinetic milestones at rates similar to euploid embryos. In contrast, aneuploid embryos, especially those with mosaicism, exhibit marked developmental delays at later stages (t7, t8, tM, tB). Full article

Background/Objectives: Large-scale (epi)genomic studies have substantially advanced our understanding of the molecular landscape of meningiomas, most recently embedded in the cIMPACT-NOW update 8. As a result, molecular data are increasingly integrated into risk-adapted treatment algorithms. However, it remains uncertain to what extent non-invasive MRI can capture underlying molecular variation and risk. Methods: We assembled a large, single-institution cohort of 225 newly diagnosed meningiomas (WHO grades 1–3) with available preoperative MRI, as well as comprehensive epigenome-wide methylation and copy-number profiling. Tumors were segmented into core and edema regions using a state-of-the-art automated pipeline from the BraTS challenge. Radiomic features were extracted and used to train Random Forest classifiers to predict WHO grade, molecular risk, and specific alterations such as 1p loss in a hold-out test set. Results: Our models achieved accuracy above 91% for integrated molecular risk classification, 87.5% for 1p chromosomal status, and 76.8% for WHO grade prediction, with corresponding AUCs of 0.91, 0.90, and 0.89, underscoring the robustness of radiomic features in capturing histopathological and, especially, molecular characteristics. Conclusions: Preoperative MRI effectively captures the underlying molecular biology of meningiomas and may enable rapid molecular assessment to inform decision-making and prioritization of confirmatory testing. However, it is not yet ready for clinical use, showing lower accuracy for current WHO grade classification. Full article

Background/Objectives: Uterine leiomyomas (ULs) and breast fibroadenomas (FAs) are the most common benign tumors in women, both arising in hormone-responsive mesenchymal tissues and often co-occurring during reproductive years. Despite their shared hormonal sensitivity and frequent MED12 mutations, their downstream molecular evolution remains poorly characterized. This study aimed to investigate whether ULs and FAs, though initiated by similar genetic alterations, diverge in their oncogenic trajectories, thereby addressing the molecular basis for their distinct clinical behaviors. Methods: We performed whole-exome sequencing (WES) on 15 uterine leiomyomas and 7 publicly available fibroadenomas with matched normal controls to compare somatic mutations, copy number alterations (CNAs), and mutational signatures. All UL samples were derived from Korean patients who underwent surgical treatment at a tertiary hospital between 2017 and 2019. Somatic variants were analyzed using MuTect2 and Strelka2. FACETS was used to estimate copy number changes in individual samples, and GISTIC2 to identify recurrent and statistically significant copy number alterations across patient cohorts. Mutational processes were inferred using SigProfiler. Microsatellite instability status was determined with MSIsensor2. The study was approved by the Institutional Review Board (UC17SNSI0092). Results: Comparative whole-exome sequencing of 15 ULs and 7 FAs from matched tumor-normal samples in an East Asian cohort confirmed both tumor types harbor identical MED12 p.G44D mutations, establishing shared molecular initiation. However, post-initiation evolution diverged dramatically: ULs exhibited chromosomal instability with 15 copy number amplifications, 6 of which affected oncogenes, but relatively modest point mutations. In contrast, FAs remained chromosomally stable but hypermutated, harboring 1.47× more variants than ULs despite lower tumor purity. Notably, one histologically benign FA harbored multiple loss-of-function mutations plus an EGFR gain-of-function mutation typically associated with malignant breast cancer, challenging traditional benign-malignant classifications. Conclusions: Despite sharing a common initiating mutation in MED12, ULs and FAs evolve through fundamentally distinct genomic pathways. UL evolves through chromosomal instability, whereas FA evolves through a mutator phenotype, with important implications for understanding tumor biology and molecular-based risk stratification. These findings support a paradigm of tissue-specific oncogenic evolution and underscore the potential clinical utility of genomic profiling in distinguishing benign tumors with atypical molecular features. Full article

Background/Objectives: X-linked intellectual disability (XLID) is a highly heterogeneous disorder accounting for ~10% of all males with ID. Next-generation sequencing (NGS) has revolutionized the discovery of causal XLID genes and variants; however, many cases remain unresolved. We present a four-generation syndromic XLID family with multiple males exhibiting variable degree of ID, focal dystonia and epilepsy. Methods: Extensive cytogenetic and targeted genetic testing was initially performed, followed by whole-exome sequencing (WES) and short-read whole-genome sequencing (WGS). Apart from the routine NGS analysis pipelines, sequencing data was revisited by focusing on poorly covered/mapped regions on chromosome X (chrX), to potentially reveal unidentified clinically relevant variants. Candidate variant validation and family segregation analysis were performed with Sanger sequencing. Results: All initial diagnostic testing was negative. Subsequently, 300 previously reported “dark” chrX coding DNA sequences, overlapping 97 genes, were cross-checked against 29 chrX genes highly associated (p < 0.05) with ID and focal dystonia, according to Phenomizer. Manual inspection of the existing NGS data in two low-coverage regions, chrX:25013469-25013696 and chrX:111744737-111744820 (hg38), revealed a recurrent pathogenic ARX variant NM_139058.3:c.441_464dup p.(Ala148_Ala155dup) (ARXdup24) associated with non-syndromic or syndromic XLID, including Partington syndrome. Sanger sequencing confirmed ARXdup24 in all affected males, with carrier status in their unaffected mothers, and absence in other unaffected relatives. Conclusions: After several years of diagnostic odyssey, the pathogenic ARXdup24 variant was unmasked, supporting a genotype–phenotype correlation in the first Partington syndrome family in Cyprus. This study highlights that re-examining underrepresented genomic regions and using phenotype-driven tools can provide critical diagnostic insights in unresolved XLID cases. Full article

Background: The androgen receptor (AR) is a ligand-dependent transcription factor of the nuclear steroid receptor superfamily, implicated in the pathogenesis of various solid tumors. The AR gene, located on chromosome Xq11–12, is accompanied by several X-linked genes that modulate AR expression and function, including FLNA, UXT, and members of the melanoma antigen gene (MAGE) family (MAGEA1, MAGEA11, MAGEC1, MAGEC2). While the AR has been investigated in multiple tumor types, its role in adult-type diffuse gliomas remains largely unexplored. Here, we characterized AR protein expression and the promoter methylation status of the AR and associated regulatory genes in adult-type diffuse gliomas. Methods: A retrospective analysis was conducted on 50 patients with adult-type diffuse gliomas, including IDH-mutant gliomas (grades 2–4) and IDH-wildtype glioblastomas (GBMs), classified according to the 2021 WHO criteria. AR nuclear expression was assessed by immunohistochemistry (IHC). Methylation-specific PCR and quantitative DNA methylation analyses were employed to evaluate promoter methylation of the AR and selected co-regulatory genes. Results: AR nuclear positivity correlated significantly with male sex (p = 0.04) and higher tumor grade, with the highest expression in IDH-wildtype GBMs (p = 0.04). In IDH-mutant gliomas, AR immunoreactivity was more prevalent in astrocytomas than in 1p/19q codeleted oligodendrogliomas (p = 0.02). AR expression was associated with unmethylated MGMT promoter status (p = 0.02). DNA methylation analysis revealed AR gene hypomethylation in tumors displaying nuclear AR positivity and in IDH-wildtype GBMs (Kruskal–Wallis p < 0.05). Additionally, methylation patterns of AR co-regulators located on the X chromosome suggest epigenetic regulation of AR signaling in gliomas. Conclusions: The findings reveal distinct AR pathway activation patterns in adult-type diffuse gliomas, particularly IDH-wildtype GBMs, suggesting that further exploration of antiandrogen therapies is warranted. Full article

Background: In vitro fertilization (IVF) has become a widely used method of assisted reproduction. However, concerns remain regarding the potential genotoxic effects of ovarian stimulation protocols used during IVF, especially in relation to cervical epithelial cells. The micronucleus (MN) assay is a validated cytogenetic biomarker of chromosomal damage and genome instability, increasingly utilized in cancer risk assessment. This study aimed to evaluate the genotoxic effect of IVF treatment on cervical epithelial cells in infertile women by comparing MN frequency before and after IVF cycles and with matched healthy controls. Methods: This prospective observational study included 15 women undergoing IVF and 15 age-matched healthy controls. All IVF participants had primary infertility and were undergoing their first IVF/ICSI cycle. Cervical smear samples were collected from the IVF group before and three months after treatment failure. MN assay was applied, and cytogenetic parameters (MN, binucleated cells, broken egg cells, and budding cells) were evaluated under light microscopy. Non-parametric statistical tests were used for analysis. Results: A statistically significant increase in MN frequency was found in the IVF group following treatment compared to pre-treatment samples and the control group (p = 0.001). HPV status was not assessed during the study period and is acknowledged as a key limitation. However, no significant differences were observed in other nuclear anomalies. Pre-treatment MN frequencies were not significantly different from those in controls. Conclusions: The findings suggest a potential cytogenetic impact of IVF-related hormonal stimulation on cervical epithelial cells, as evidenced by increased MN frequency. While no direct clinical implications were identified, these changes warrant further investigation into the long-term genomic safety of assisted reproductive technologies. Full article

Acute lymphoblastic leukemia (ALL) remains a formidable therapeutic challenge, particularly within high-risk cohorts. Advances in next-generation sequencing have elucidated critical mutations that significantly influence prognosis and therapeutic decision-making. Tyrosine kinase inhibitors (TKIs) have significantly improved treatment outcomes in Philadelphia chromosome-positive (Ph+) ALL. Meanwhile, emerging therapies such as monoclonal antibodies and chimeric antigen receptor (CAR) T-cell therapies show promise for B-cell ALL, although they are associated with considerable toxicities. These developments underscore the persistent need for alternative therapeutic strategies that can benefit a wider range of patients. In this study, human ALL cell lines—characterized by either wild-type or mutant tumor protein p53 (TP53) status—were treated with RG7388 (an MDM2 (mouse double minute 2 homolog) inhibitor) and BBI608 (a STAT3 (signal transducer and activator of transcription 3) inhibitor), both as single agents and in combination. Cell viability was quantified using XTT assays, while apoptosis was assessed via flow cytometry. Additionally, immunoblotting and qRT-PCR were employed to evaluate changes in protein and gene expression, respectively. RG7388 demonstrated potent growth inhibition in the majority of ALL cell lines, with p53-mutant cell lines exhibiting resistance. BBI608 reduced cell viability across all tested cell lines, though with variable sensitivity. Notably, the combination of RG7388 and BBI608 elicited synergistic anti-proliferative effects in p53 wild-type and partially functional p53-mutant cells, enhancing apoptosis and stabilizing p53 protein levels. In contrast, MOLT-4 cells, which harbor concurrent TP53 and STAT3 mutations, did not benefit from the combination treatment, indicating an inherent resistance phenotype within this subset. Collectively, these findings highlight the therapeutic potential of combined MDM2 and STAT3 inhibition in ALL, particularly in p53 wild-type and partially functional p53-mutant contexts. This combinatorial approach augments apoptosis and tumor growth suppression, offering a promising avenue for expanding treatment options for a broader patient population. Further investigation is warranted to validate these preclinical findings and to explore translational implications in genetically diverse ALL subsets. Full article

Background: Recently, vitamin D deficiency (VDD) has been described as a pandemic, affecting all groups of the population. Pregnant women and preterm infants are particularly vulnerable to vitamin D deficiency. Objectives: We aimed to evaluate the maternal and neonatal vitamin D status in relation with maternal vitamin D supplementations during pregnancy and to identify demographic, social, and healthcare risk factors for maternal VDD and vitamin D insufficiency in women delivering at ≤32 weeks of gestation. Methods: This prospective observational study was developed in the regional level III maternity unit of the Clinical County Emergency Hospital Sibiu. It included all admitted mothers who delivered at ≤32 weeks of gestation and their infants between 1 March 2022 and 28 February 2025. Infant deaths in the first 24 h of life, major congenital defects, chromosomal abnormalities, the admission of outborn infants without their mothers, or the transfer of the mother more than 48 h after birth were used as exclusion criteria. Maternal and neonatal data were collected from medical records. Data on maternal vitamin D supplementation were collected through interviews. Univariate and multivariate logistic regressions, linear regression, and predictive models were performed for data analysis. Results: A total of 146 mothers (median (IQR) age 30 (24–35) years) and their 164 preterm infants born at ≤32 weeks of gestation (median gestational age of 30 (27–31) weeks and birth weight of 1200 (900–1527) g) were included in this study. Only 43.15% of the mothers used multivitamins containing vitamin D during pregnancy, and 10.96% used specific vitamin D supplements. Vitamin D supplementation was used for a median of 4 (3–5) months at a median dose of 800 (250–1500) IU/day. Severe VDD (25(OH)D < 10 ng/mL), VDD (25(OH)D < 20 ng/mL), VDI (25(OH)D 20–29 ng/mL) were found in 19.86%, 55.48%, and 23.97% of the mothers and 16.46%, 58.53%, and 25.61% of their infants, respectively. A significant correlation was found between the maternal and neonatal status (r = 0.684, r² = 0.468, p < 0.001, B = 0.62). Both the maternal and neonatal vitamin D status were correlated with the vitamin D duration and dose used for supplementation during pregnancy. The logistic regression analysis showed that birth during a cold season and increased parity are independently associated with severe maternal VDD, while birth during the cold season and a lower educational status were independently associated with maternal VDD. Only an absent vitamin D supplementation (in the form of a multivitamin or specific vitamin D supplements) has been proven as an independent risk factor for VDI. Conclusions: Our findings revealed a worrisome prevalence of severe VDD, VDD, and VDI in mothers delivering very prematurely and in their infants. Additionally, less than half of the mothers in this study used vitamin D supplements during pregnancy despite the national recommendations. The professionals involved in advising pregnant women and policymakers should find solutions to improve the vitamin D status in these vulnerable groups of the population. Full article

The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, a well-established event in prostate carcinogenesis. This study investigates whether LPL deletion represents a biologically relevant event or occurs merely as a bystander to NKX3.1 loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed LPL deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of NKX3.1 and LPL in 54 patients. Notably, NKX3.1 loss without accompanying LPL deletion was observed in eight additional cases. These findings suggest that LPL deletion is a passenger event secondary to NKX3.1 loss and underscore the importance of cautious interpretation of cytogenetic findings involving the LPL locus. Full article

Background: Kleefstra syndrome 1(KLEFS1, OMIM#610253) is a rare neurodevelopmental disorder (NDD) instigated by heterozygous variants or microdeletions occurring in the 9q34.4 genomic region of the euchromatic histone methyltransferase-1 (EHMT1) gene and is inherited in an autosomal dominant (AD) manner. The clinical phenotype of KLEFS1 includes moderate to severe intellectual disability (ID), hypotonia, and distinctive facial features and additionally involves other organ systems (heart, renal, genitourinary, sensory) albeit with phenotypic heterogeneity between patients. The purpose of this study is to expand the genotypic spectrum of KLEFS1 and compare phenotypic features of the syndrome of already published cases. Methods: Exome sequencing (ES), chromosomal microarray analysis (CMA), as well as sanger sequencing, for confirmation of the de novo status of the frameshift variant, were used. Results: Here we describe two more cases, both males with a similar age and carriers of novel variants; one with a frameshift variant involving exon 13: p.Val692Glyfs*64 and the other with the smallest so far described, 11 Kb (exons 19-25), 9q34.4 microdeletion: 9q34.3 (140703393-140714454). Both presented with an NDD disorder with one showing more severe ID with significant social disabilities, while the other with the microdeletion had mild ID and following a normal education curriculum. Neither of them were obese nor had any other significant organ system disorder. Conclusions: The observed phenotypic variability due to genotypic differences in the two children contributes to the expanding spectrum of KLEFS1 disease phenotypes. Full article

Background: Fluorescence in situ hybridization (FISH) testing against chromosome 12 centromere (CEN12) is routinely included in the work-up of patients with suspected chronic lymphocytic leukemia (CLL) or monoclonal B-cell lymphocytosis (MBL). However, incidental findings can occur and be challenging. Methods: Interphase and metaphase FISH analyses with various probes, including CEN12 probes from different vendors, and conventional cytogenetics were applied. Results: A CLL FISH panel was performed at the clinician’s request on a peripheral blood specimen from a 55-year-old female with fluctuating leukocytosis and lymphocytosis for over six years. An additional diminished CEN12 FISH signal was observed in approximately 70% of the nucleated cells analyzed. Concurrent flow cytometry excluded a diagnosis of CLL or MBL, and karyotyping exhibited a normal female karyotype. Further studies excluded potential cross-hybridization due to limited specificity of the CEN12 probes and revealed the location of the additional diminished CEN12 signal on the centromere of one chromosome 16 homolog (CEN16), without other material from the short arm (12p) or long arm (12q) of chromosome 12 being involved. Conclusions: This is the first case with an “uncertain” trisomy 12 status, presenting a challenge to clinical cytogenetic diagnosis. Although the mechanism for this mosaic “partial trisomy 12” and its clinical impact remain unknown, this case highlights the importance of further investigation using orthogonal methods to clarify incidental findings during diagnostic practice. Full article

Exposure to low-dose ionizing radiation in occupational settings raises concerns about chromosomal aberrations (CAs) and their potential impact on genomic stability. Copy number variations (CNVs), structural genomic changes, influence susceptibility to environmental stressors and radiation-induced damage. This study analyzed CAs in 180 nuclear power plant workers exposed to occupational radiation and 45 controls, stratified by GSTM1 and GSTT1 CNVs. Workers exhibited significantly higher frequencies of chromatid-type and chromosome-type aberrations, of 5.47 and 3.01 per 500 cells, respectively, compared to 3.57 and 0.64 in controls (p < 0.001 for both). In the relatively high-exposure group, chromatid-type aberrations decreased with increasing GSTM1 and GSTT1 copy numbers. For GSTM1, individuals with zero copies showed 6.37 ± 3.47 aberrations per 500 cells, compared to 5.02 ± 3.05 for one copy and 4.67 ± 2.40 for two or more copies (p = 0.06). A similar trend was observed for GSTT1, with 6.00 ± 3.29 aberrations per 500 cells for zero copies, 5.38 ± 2.79 for one copy, and 4.11 ± 4.26 for two or more copies (p = 0.05). Poisson regression analysis further supported these findings after adjusting for potential confounders such as age, smoking status, and alcohol intake. Workers with null genotypes exhibited a 1.36-fold increase in chromatid-type aberrations compared to those with higher copy numbers under relatively high-exposure conditions, suggesting a synergy effect between GSTM1 and GSTT1 null genotypes in modulating radiation-induced aberrations. These findings underscore the role of genetic susceptibility, particularly involving GSTM1 and GSTT1 CNVs, in modulating radiation-induced chromosomal damage. The observed gene–environment interaction in the relatively high-exposure group suggests that pre-existing CNVs contribute to chromosomal instability under radiation exposure. Full article