Radiotherapy outcome is governed by radiosensitivity and DNA repair capacity of tumour cells and their interaction with surrounding normal tissues and vice versa. As radiosensitivity varies with the origin and genetic makeup of the cell, this study compares direct and bystander responses in directly targeted to X-rays and non-targeted (bystander) tumour (MCF-7 and PC3) and normal (MCF10A and HPrEC) epithelial cells of breast and prostate origin. Cells were exposed to X-rays (0, 2, and 4 Gy) by a clinical LINAC and co-cultured with corresponding un-irradiated cells. Micronucleus (MN) and clonogenic assays were adopted to quantify the DNA damage and survival fraction (SF), respectively, in all cells and Multicolour fluorescence in situ hybridization (m-FISH) in MCF-7 and PC3 cells to identify the chromosomes frequently involved in translocations. Directly targeted tumour and normal cells showed a significant increase in MN frequency and decrease in SF. MN frequency increased from 0.023 ± 0.004 (control) to 0.076 ± 0.008 (2 Gy), and 0.177 ± 0.013 (4 Gy) in MCF-7 cells. MCF10A showed MN frequency of 0.049 ± 0.007 (control), 0.128 ± 0.011 (2 Gy) and 0.219 ± 0.014 (4 Gy). SF was significantly higher in MCF-7 (0.39 ± 0.03 and 0.15 ± 0.02) cells than MCF10A (0.30 ± 0.02 and 0.12 ± 0.01). MN frequency in PC3 cells increased from 0.056 ± 0.007 (control) to 0.168 ± 0.012 (2 Gy) and 0.378 ± 0.019 (4 Gy). HPrEC exhibited MN frequency of 0.018 ± 0.004 (control), 0.058 ± 0.007 (2 Gy), and 0.147 ± 0.012 (4 Gy). SF was higher in HPrEC (0.72 ± 0.03 and 0.40 ± 0.02) cells than PC3 (0.22 ± 0.01 and 0.09 ± 0.004). Similarly, a significant increase in MN frequency was observed in the non-targeted cells when compared to that of control, confirming occurrence of radiation-induced bystander effect. Thus, the results indicate radiation sensitivity differs among the cell types. The m-FISH results reveal a non-random distribution of X-irradiation induced breaks and translocation. In directly targeted cells, chromosomes 7, 16, 17, 20, 21, 22 (MCF-7) and 3, 4, 6, 14, 17 (PC3) showed frequent involvement in translocations. Chromosomes 3, 4, 6, and 14 (MCF-7) and 10, 11, 17, and 18 (PC3) were frequently involved in non-targeted cells. The present study results indicate that the tumour cells demonstrated higher radiosensitivity and a stronger bystander response than normal cells. Intrinsic molecular factors and genome organization affect both targeted and non-targeted responses, emphasizing their relevance for optimizing radiotherapy strategies.

Cytogenetic findings are critical for determining prognosis, therapy and risk assessment in acute lymphoblastic leukaemia (ALL). Data on the epidemiology of cytogenetic findings in ALL from southern Asia is limited. This report documents the cytogenetic changes in ALL seen at a referral hospital in southern India and compares it with the literature. Clinical profiling and conventional cytogenetic analysis (CCA) of all patients with reverse-transcription polymerase chain reaction (RT-PCR) for detection of cryptic t(12;21). Of 1968 ALL, 1,819 (92.4%) patients, age 0.3-84 years, (median 17) had successful CCA. There were 979 children (<18 years) and 840 adults. Abnormal karyotypes were found in 1368 (75.2%), B-ALL-78% and T-ALL-69%. Favorable-risk group included high hyperdiploidy (HeH, 17.4%), t(12;21) (9.8%), and t(1;19) (4.3%), with > 80% of HeH and t(12;21) in children. The unfavorable-risk group included t(9;22) (11.2%, 80% adults), hypodiploidy (8.0%), MYC (8q24) translocations (2.3%), and KMT2A/MLL(11q23) translocations (1.6%). In children, the frequency of HeH (26.8%) was lower than the West (30.7%) but higher than S.E. Asia (15.5%) while t(9;22) (4.2%) was higher than the West (2%) but lower than S.E. Asia (6.8%). In adults, frequencies again differed from S.E. Asia (HeH, 6.4% vs. 2.7% and t(9;22), 19.4% vs. 29.3%) but were comparable to the West. CCA effectively provides diagnostic information in over 90% of ALL cases. While the spectrum of cytogenetic changes is similar to global data, there are significant regional variations in the frequencies of specific abnormalities.

Homoeologous chromosomes within the grass tribe Triticeae have largely retained their cross-species colinearity. However, prior studies suggest that the karyotype of Aegilops uniaristata, a diploid wild relative of wheat (genome NN, 2n=2x=14), is noticeably different from most of the Triticeae species. We used fluorescence in situ hybridization with a large collection of probes hybridizing to repetitive and coding regions of the Triticeae genomes to perform comparative cytogenetic analysis and establish the macrostructure of Ae. uniaristata chromosomes. Compared to wheat, all chromosomes of Ae. uniaristata, with the exception of 5N, were found significantly rearranged due to multiple inter- and intrachromosomal translocations and inversions. Discussion/ Conclusion: The N genome structure revealed in our study is useful for understanding karyotype evolution and facilitating introgression from Ae. uniaristata and the N genome of polyploid Aegilops species for wheat improvement.

Introduction MECOM rearrangements are frequently observed in myeloid neoplasms and associated with poor prognosis. Among the genomic alterations leading to MECOM rearrangements, t(2;3)(p13~p25;q26.2) accounts for approximately 13% of reported cases. However, the precise DNA breakpoints of this translocation have not been previously reported, nor has the mechanism by which it alters MECOM expression been fully elucidated. In this report, we describe two cases with myelodysplastic syndromes (MDS) and t(2;3)(p23;q26.2). Our genomic characterization of these two t(2;3) translocations provided insights into the molecular mechanism of MECOM activation. Case Presentation Case 1 is a 44-year-old female presented with new anemia and thrombocytopenia. She was treated with azacitidine. After two allogeneic stem cell transplants, her disease relapsed with rapid progression to acute myeloid leukemia (AML). Patient passed away one year after progression to AML and eight years after initial diagnosis. Case 2 is a 75-year-old female who was incidentally found to have macrocytic anemia with rare circulating blasts. She remained asymptomatic from anemia and did not require transfusions or treatment. Her disease progressed to MDS with excess blasts three years later. Patient was treated with azacitidine. Fifteen months later, her disease further progressed to AML. She passed away five months later and four and a half years after initial diagnosis. DNA sequencing analysis of these two cases revealed that the t(2;3)(p23;q26.2) breakpoints were within the regulatory regions of ZFP36L2 and THADA on chromosome 2 and the proximity of MECOM on chromosome 3, creating a novel regulatory configuration for MECOM. Notably, the translocation breakpoints differed by 270 kb on chromosome 2 and 93 kb on chromosome 3, resulting in distinct translocated regulatory elements with varying sizes and proximities to MECOM. These structural differences may influence the level of MECOM upregulation and contribute to variation in disease severity and progression. Conclusion Our findings highlighted that, despite cytogenetic similarity, different t(2;3) translocations may exert distinct regulatory effects depending on the precise breakpoint locations. Thus, molecular characterization of MECOM rearrangements is critical for understanding disease pathogenesis and prognosis in myeloid neoplasms and may lead to the development of novel treatment.

IIntroduction Radioiodine (131I) is commonly used for the treatment of hyperthyroidism and for differentiated thyroid cancer (DTC) as an ablative therapy. Radioiodine (131I) constitutes almost 90% of the therapies that are currently performed in the nuclear medicine field. In this study, retrospective cytogenetic follow up analysis was performed after 29 years (2023) and 30 years (2024) in a papillary thyroid cancer patient who received the second round of 131I treatment in 1994. Methods Metaphase chromosomes prepared from the in vitro culture of peripheral blood lymphocytes of the patient were utilized for the analysis of unstable (dicentrics and fragments) and stable chromosome aberrations (simple, complex and clonal). For dicentric chromosome detection, fluorescence in situ hybridization FISH) was performed using human centromere and telomere specific peptide nucleic acid probes. Chromosome translocations were detected by a cocktail of DNA probes for individual chromosomes (1, 2 and 4) and multicolor FISH probe for the entire human genome. Micronuclei were analyzed by cytokinesis block micronucleus assay. Absorbed radiation dose was estimated at 95% confidence intervals from the frequencies of chromosome aberrations (dicentric chromosomes and translocations) using correlation coefficients of the γ-rays dose response curve using the DoseEstimate_v5.1 algorithm. Results The percentage of cells with stable and unstable chromosome aberrations remained the same (~8%) in the patient during the entire retrospective study albeit variations in the frequencies of reciprocal and non-reciprocal translocations. The frequency of color junctions (chromosome exchange events) detected by the multicolor FISH technique showed a sharp increase in this study (0.33/cell) compared to our earlier study (0.19/cell). The persistence of clonal translocation involving chromosomes 14;15 was observed in 1-1.6% of the total cells analyzed. In the 29-year follow up study, one complex translocation involving chromosomes 1, 9 and 14 was detected by mFISH in a total of 200 cells. Discussion Our findings indicate that the past internal therapeutic exposure of radioiodine results in long-lasting chromosomal damage and the retrospective study of this nature will be useful for monitoring the progression of any oncogenic events driven by chromosomal instability in the hematopoietic system of 131I therapy patients.

In ISCN 2024: An International System for Human Cytogenomic Nomenclature [Cytogenet Genome Res 2024;164(suppl 1); https://doi.org/10.1159/000538512 and https://doi.org/10.1159/isbn.978-3-318-07331-7] by Hastings RJ, Moore S, Chia N (editors), the following corrections to the ISCN should be noted. Please contact the ISCN Standing Committee via the forum if you identify any additional errata.In Chapter 4, Section 4.2.1 Chromosome Abnormality Description Rules, Rule f, the lineNeoplasia: 46,XX,t(9;22)(q34;q11.2)[10]/47,XX,t(9;22),+der(22)[10]Should correctly read:Neoplasia: 46,XX,t(9;22)(q34;q11.2)[10]/47,XX,t(9;22),+der(22)t(9;22)[10]In Chapter 4, Section 4.5.3k Nomenclature for Clones, Mosaics and Chimeras, the linesRelated neoplastic clones: 46,XX,del(7)(q22),+8[10]/46,XX,i(7)(q10),+8[12]Should correctly read:Related neoplastic clones: 47,XX,del(7)(q22),+8[10]/47,XX,i(7)(q10),+8[12]Related neoplastic clones: 46,XY,del(5)(q13q31),-7[3]/46,XY,del(5)(q13),-7[17]Should correctly read:Related neoplastic clones: 45,XY,del(5)(q13q31),-7[3]/45,XY,del(5)(q13),-7[17]In Chapter 5, Section 5.5.3 Derivative Chromosomes, Rule c, example iv, the lineThe additional derivative chromosome 4 is listed before the translocation following the chromosome order rule (see Section 4.3)Should correctly read:The additional derivative chromosome 4 is listed before the translocation following the alphabetical order rule (see Section 4.3)In Chapter 5, Section 5.4.1 Specification of Chromosomes and Breakpoints, Rule eAlternatively, uncertainty of breakpoints may be indicated by a question mark (?), e.g., 1p1? (see Section 4.2.1) or by a tilde (∼), e.g., 1p34∼p35 (see Section 4.2.1)Should correctly read:Alternatively, uncertainty of breakpoints may be indicated by a question mark (?), e.g., 1p1? (see Section 4.2.1) or by a tilde (∼), e.g., 1p35∼p34 (see Section 4.2.1)In Chapter 5, Section 5.4.1 Specification of Chromosomes and Breakpoints, Rule hIf the rearrangement involves a single chromosome the breakpoints are not separated by a semicolon (;), e.g., inv(2)(p23q11.2), del(4)(p15.3p16.1), r(18)(p11.2q23)Should correctly read:If the rearrangement involves a single chromosome the breakpoints are not separated by a semicolon (;), e.g., inv(2)(p23q11.2), del(4)(p16.1p15.3), r(18)(p11.2q23)In Chapter 5, Section 5.4.2 Karyotype format for Designing Structural Chromosome Abnormalities, Rule b, example i, the textThe abnormal chromosome 11 has resulted from a complex translocation involving chromosomes 5, 8 and 11, t(5;8;11;5)(q23;q24.1;q12;q11.2)Should correctly read:The abnormal chromosome 11 has resulted from a complex translocation involving chromosomes 5, 8 and 11, der(11)t(5;11)(q11.2;q12)t(5;8)(q23;q24.1)In Chapter 5, Section 5.5.9.2 Insertion between Two Chromosomes, Rule a, the linea. Interchromosomal insertions (ins) are three-break rearrangements in which part of one chromosome is inserted at a point of breakage in the same or another chromosomeShould correctly read:a. Interchromosomal insertions (ins) are three-break rearrangements in which part of one chromosome is inserted at a point of breakage in the homologous or another chromosomeIn Chapter 5, Section 5.5.11 Isochromosomes, Rule e, example v, the noteNote: if homozygosity for the long arm of chromosome 21 is not proven, an alternative description using der(21)(q10;q10) should be used (see Section 5.5.18.3)Should correctly read:Note: if homozygosity for the long arm of chromosome 21 is not proven, an alternative description using der(21;21)(q10;q10) should be used (see Section 5.5.18.3)In Chapter 5, Section 5.5.15 Recombinant chromosomes, Rule d, example ii46,XX,rec(21)del(21)ins(21)(p13q22.2q22.3)dpator46,XX,rec(21)(pter->q22.2::p22.3->qter)dpatShould correctly read:46,XX,rec(21)del(21q)ins(21)(p13q22.2q22.3)dpator46,XX,rec(21)(pter->q22.2::p22.3->qter)dpatIn Chapter 5, Section 5.5.15 Recombinant chromosomes, Rule d, example iii46,XY,rec(1)dup(5q)ins(1;5)(q32;q11.2q22)dinh,der(5)ins(1;5)dinh46,XY,rec(1)(1pter->1q32::5q11.2->5q22::5q22->5qter)dinh,der(5)(5pter->5q11.2::5q22->qter)dinhShould correctly read:46,XY,rec(1)dup(5q)ins(1;5)(q32;q11.2q22)dinh,der(5)ins(1;5)dinhor46,XY,rec(1)(1pter->1q32::5q11.2->5q22::5q22->5qter)dinh,der(5)(5pter->5q11.2::5q22->qter)dinhIn Chapter 5, Section 5.5.16.2 Ring Chromosomes Derived from More than One Chromosome, Rule h, the line50,XX,+1,+3,+8,+r and 50,XX,+1,+3,+8,+r+marShould correctly read:50,XX,+1,+3,+8,+r and 51,XX,+1,+3,+8,+r,+marIn Chapter 6.3.4 Clonal Evolution, Rule f, example xvi, the lineAlternatively, the ISCN could be written in full for clarity:46,XY,-2,-9,add(10)(q26),del(20)(q11.2q13.3),+mar1,+mar2[15]/44,XY,-2,add(3)(p12),-5,+8,-9,-10,-del(20),+mar1[5]Should correctly read:46,XY,-2,-9,add(10)(q26),del(20)(q11.2q13.3),+mar1,+mar2[15]/44,XY,-2,add(3)(p12),-5,+8,-9,-10,del(20),+mar1[5]In Chapter 6.3.4 Clonal Evolution, Fig. 8. the line49,XY,t(9;22),+8,+19,+21Should correctly read:49,XY,+8,t(9;22),+19,+21In Chapter 6, Section 6.4 Rule g, example vi the NoteNote: the ten metaphases from the female donor also exhibit a constitutional t(2;5).Should correctly read:Note: the ten metaphases from the female donor also exhibit a constitutional t(2;15).In Chapter 7, Section 7.3.4.4.1 Single Chromosome Normal Signal Pattern, the linePDGFA probe signalShould correctly read:PDGFRA probe signalIn Chapter 7, Section 7.6 Mosaic and Chimera Signal Pattern, the line//nuc ish (DXZ1,DYZ3)×1[400]Should correctly read:nuc ish //(DXZ1,DYZ3)×1[400]In Chapter 8, Section 8.2.3 Inheritance, the lineWhen known, the parental origin of the abnormality may follow the copy number (x1,x3, etc.).Should correctly read:When known, the parental origin of the abnormality follows the copy number (x1,x3, etc.).In Chapter 8, Section 8.2.5 Mixed Cell Populations and Uncertain Copy Number, the lineix. 47,XY,+mar[5]/46,XY[20].ish der(2)(p11.2q13)(RP11-478D22+)[5]/2q12.1(RP11-478D22)×2[25].arr[GRCh38] 2p11.2q13(90,982,729_112,106,760)×3[0.2]Should correctly read:ix. 47,XY,+mar[5]/46,XY[20].ish der(2)(:p11.2q13:)(RP11-478D22+)[5]/2q12.1(RP11-478D22)×2[25].arr[GRCh38] 2p11.2q13(90,982,729_112,106,760)×3[0.2]In Chapter 10, Section 10.2, rule d, the line……and rsa[GRCh38] 22q11.21 (18,891,533_21,111,169)x2 (see Section 10.4.1).Should correctly read:……and rsa[GRCh38] 22q11.21(18,891,533_21,111,169)x2 (see Section 10.4.1).In Chapter 11, Section 11.4.1 Aneuploidy, the line[NC_000023.11:g.pter_qter=];[NC_000024.11:g.pter_qter[2]]Should correctly read:[NC_000023.11:g.pter_qter=];[NC_000024.10:g.pter_qter[2]].

Plain Language SummaryRobertsonian translocations (ROBs), also known as centric fusions, are chromosomal rearrangements where two chromosomes fuse by centromeres, giving rise to a large two-armed derivative chromosome. ROBs are the most common structural chromosomal rearrangements in mammals and pose medical and veterinary concern because of associated subfertility and congenital disorders, though ROBs are also of interest as a mechanism of chromosome and karyotype evolution. Robertsonian fusions are well documented in humans, mice, and cattle, but are extremely rare in horses, even though the horse karyotype has 18 acrocentric (one-armed) chromosomes, which all can potentially undergo ROB. Here, we report about the first case of ROB in the horse, whereas the affected animal was 50/50 mosaic for two different ROB cell lines: one with ROB between chromosome (Chr)17 and Chr27, another between Chr17 and Chr29, and had no cells with normal karyotype. The mare had several reproductive issues, including small ovaries, irregular estrus, and two pregnancy losses – clinical features which are consistent with ROBs in other species. Besides presenting the first ROB in the horse and mosaicism for two different ROBs, which is extremely rare in any species, we also discuss why ROBs are frequent rearrangements in some species and extremely rare in others, regardless of the number of acrocentric chromosomes.

Introduction: In birds, males have the homogametic sex chromosomes ZZ, whereas females have the heterogametic ZW. Similar to mammalians, avian Z and W chromosomes are believed to have originated from a pair of autosomes. Over evolutionary time, the W chromosome degenerated, losing many genes. The remaining W-linked genes retain homologs on the Z chromosome. One such gene is UBAP2, which participates in cellular metabolism and signaling through the ubiquitin-proteasome pathway in mammals. However, the functions of its avian homologs, UBAP2Z (Z-linked) and UBAP2W (W-linked), remain poorly understood. To investigate the functional divergence between them in birds, we analyzed their mRNA and protein expression in embryonic gonads of Japanese quail. Methods: Using RNA-seq data of embryonic gonads of Japanese quail, contigs were generated by de novo assembly. The nucleotide sequences were predicted from the contigs by blastn analysis. Expression levels were calculated by bowtie2 and RSEM. Immunohistochemistry and Western blotting employing monoclonal antibodies specific to UBAP2Z and UBAP2W were generated to investigate protein expression and localization. Additionally, far-Western blotting was performed to examine protein-protein interactions. Results: UBAP2Z and UBAP2W nucleotide and amino acid sequences showed high similarity and shared a conserved N-terminal UBA domain. However, UBAP2W expression was consistently lower than that of UBAP2Z and showed a distinct localization pattern from UBAP2Z in embryonic gonads. In males, UBAP2Z was expressed in seminiferous tubules, while in females, it localized to the medulla. By contrast, UBAP2W was exclusively observed in the cortex of female gonads, particularly at developmental stage HH38. Furthermore, UBAP2Z and UBAP2W interacted with different binding partners, indicating divergence in their molecular function. Conclusion: These findings indicate that UBAP2W has a distinct female-specific functional role in avian gonadal differentiation. We propose that UBAP2W contributes to ovarian development and oogenesis through the ubiquitin-proteasome pathway, while UBAP2Z is involved in general cellular regulation across sexes. This study highlights functional divergence between Z- and W-linked paralogs in birds and provides new insights into sex chromosome evolution and gonadal development.

Background: Chromosomal microarray analysis (CMA) is a first-tier diagnostic test for children with unexplained developmental and/or congenital anomalies. This study aimed to evaluate the diagnostic contribution of CMA in a large, phenotypically diverse Turkish pediatric cohort. Methods: CMA was performed in 1,022 children presenting with developmental delay, intellectual disability, autism spectrum disorder, epilepsy, and/or congenital anomalies. Copy number variants (CNVs) were classified as pathogenic, likely pathogenic, or variants of uncertain significance based on American College of Medical Genetics guidelines. Results: CNVs were identified in 279 patients (27.3%), totaling 315 CNVs. Of these, 151 patients (14.8%) carried at least one pathogenic or likely pathogenic CNV, representing the diagnostic yield of the study. CNVs were more frequently classified as pathogenic when presenting as deletions. The diagnostic rate was higher among patients with syndromic features (20.2%) compared to those with isolated developmental delay/intellectual disability (11.8%). Among patients with CNVs, 139 (49.8%) exhibited phenotypes consistent with well-characterized genomic syndromes. In addition, rare but clinically significant CNVs were also identified, involving well-established dosage-sensitive genes. Notably, chromosomes X, 15, and 16 were among the most frequently affected, reflecting known genomic hotspots associated with neurodevelopmental and structural phenotypes. Conclusion: CMA is a powerful diagnostic tool in the evaluation of pediatric patients with neurodevelopmental and structural disorders. This study emphasizes the added value of high-resolution CNV detection and careful clinical phenotyping to optimize diagnostic yield and guide precision care in clinically heterogeneous pediatric populations.