[Copy number variations of CCND1 gene and chromosome 11 centromere in acral melanoma].

Objective: To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma. Methods: Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed. Results: There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level. Conclusions: CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

Silver-Russell syndrome-like features in a child with recombinant chromosome 11 derived from maternal pericentric inversion.

Silver-Russell syndrome (SRS) is a well-known syndrome but with heterogeneous etiologies. We present the case of a child with severe SRS-like features resulting from a complex rearrangement of chromosome 11 inherited from his mother. We studied the index case with karyotyping, MS-MLPA and molecular karyotyping. The mother was studied with karyotyping and subtelomeric FISH. We found a child with marked developmental delay and fatal outcome due to failure to thrive, carrying an 11p15 duplication and an 11q25 deletion of maternal origin. We discovered that the mother was a carrier of a pericentric inversion of chromosome 11, with a history of recurrence in other family members who had severe growth retardation and early death. To our knowledge, no similar SRS-like cases have been described in the literature. This report supports the importance of identification the causative genetic mechanism in SRS-like individuals with duplication in 11p15 region due to high risk of recurrence and to provide an appropriate genetic counseling to the family.

Assessment for 11q and other chromosomal aberrations in large B-cell/high-grade B cell lymphomas of germinal center phenotype lacking BCL2 expression.

The WHO classifications of hematolymphoid malignancies have recognized several distinct entities within the large B cell lymphomas, including the more recently described high-grade B cell lymphoma with 11q aberration (HGBCL-11q). We utilized genomic array to assess for chromosome 11q abnormalities in a broad set of aggressive B cell lymphomas from 27 patients with a focus on younger adults. The findings suggest more frequent alterations of 11q in diffuse large B cell lymphoma (DLBCL)/HGBCL-GC BCL2-, in comparison to cases of Burkitt lymphoma (BL) or DLBCL-GC BCL2+, and confirm a low genomic complexity score of BL. Variability identified in patterns of 11q alterations suggests genomic array studies may afford value over FISH testing as we continue to understand HGBCL-11q as a distinct entity, and interrogate cases of DLBCL/HGBCL-GC BCL2-.

Correlation of Cerebrospinal Fluid Total Protein and Serum Neutrophil-to-Lymphocyte Ratio with Clinical Outcomes of Guillain-Barre Syndrome Variants.

OBJECTIVE: To evaluate the correlation of cerebrospinal fluid total protein and serum neutrophil-to-lymphocyte ratio with the clinical outcomes and the various clinical and electrophysiological variants of Guillain-Barre syndrome. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Department of Neurology, Mayo Hospital and King Edward Medical University, Lahore, Pakistan, from November 2022 to April 2023. METHODOLOGY: Fourty-six Guillain-Barre syndrome patients, aged 12-70 years, were included in the study diagnosed by using the Brighton's criteria. Functional disability and respiratory insufficiency were assessed by using the modified Hughes disability score and the Erasmus Guillain-Barre syndrome respiratory insufficiency score, respectively. Serum neutrophil-to-lymphocyte ratio and cerebrospinal fluid total protein were calculated for each patient at the time of admission. RESULTS: Axonal variants had a higher mean neutrophil-to-lymphocyte ratio (5.29 ± 4.38) than demyelinating variants (4.71 ± 3.4) and Miller-Fischer syndrome (3 ± 2.828). This ratio was positively correlated with the modified Hughes's disability score (r = 0.790, p = 0.001) and the Erasmus Guillain-Barre syndrome respiratory insufficiency score (r = 0.936, p = 0.002). Mean cerebrospinal fluid total protein was higher for demyelinating (218 ± 136 mg/dl) than axonal variants (86 ± 56 mg/dl) and Miller-Fischer syndrome (34 ± 21 mg/dl). However, higher modified Hughes disability score (4-6) (r = 0.020, p = 0.117) and a high Erasmus Guillain-Barre syndrome respiratory insufficiency score (5-7) (r = 0.115, p = 0.302) did not significantly affect mean cerebrospinal fluid total proteins. CONCLUSION: Serum neutrophil-to-lymphocyte ratio can be regarded as a reliable biomarker to assess disease severity and clinical outcome in Guillain-Barre syndrome. Cerebrospinal fluid total protein is a poor predictor of the prognosis and severity of Guillain-Barre syndrome. KEY WORDS: Guillain-Barre syndrome (GBS), Clinical outcome, Cerebrospinal fluid total protein (CSF-TP), Neutrophil-to-lymphocytic ratio (NLR), Prognostic biomarker.

Fertility-Sparing Surgery and Adjuvant Chemotherapy with Trastuzumab Result in Complete Remission in a Young Woman with Rare Primary Mucinous Ovarian Cancer due to ERBB2 Co-amplification with CDK12 and Chromosome 11q13.3 Amplicon: A Case Report and Literature Review.

Primary mucinous ovarian carcinoma (PMOC) is a rare tumor, accounting for approximately 3% of all epithelial ovarian cancers (EOCs), with clinical risk factors and biologic features distinct from that of EOC. The prognosis for women with recurrent and high-grade PMOC remains poor, likely related to a poor response to conventional chemotherapy for EOC. A 27-year-old Chinese woman sought medical attention in January 2021 for abdominal distention from a large pelvic mass. After extensive investigations and workup, she was diagnosed with PMOC of the right ovary. Following multidisciplinary team (MDT) discussions, the patient underwent fertility-sparing surgery (FSS) (abdominal left adnexectomy, right partial oophorectomy, pelvic lymph node dissection, para-aortic lymph node dissection, omentectomy) as she yearned to preserve her fertility and the contralateral ovary appeared normal. Deep genetic analyses revealed ERBB2 co-amplification with CDK12 and chromosome 11q13.3 amplicon. Treatment with fertility-sparing surgery and adjuvant chemotherapy with trastuzumab results in complete remission. This novel strategy utilizing precise diagnostics and characterization of the histo-type of rare tumors allowed personalized targeting with optimum drug response for women who yearn fertility preservation and remission from the disease, especially when there is very limited clinical experience on management of such rare ovarian tumors.

Olfactory receptor genes and chromosome 11 structural aberrations: Players or spectators?

The largest multi-gene family in metazoans is the family of olfactory receptor (OR) genes. Human ORs are organized in clusters over most chromosomes and seem to include >0.1% the human genome. Because 369 out of 856 OR genes are mapped on chromosome 11 (HSA11), we sought to determine whether they mediate structural rearrangements involving this chromosome. To this aim, we analyzed 220 specimens collected during diagnostic procedures involving structural rearrangements of chromosome 11. A total of 222 chromosomal abnormalities were included, consisting of inversions, deletions, translocations, duplications, and one insertion, detected by conventional chromosome analysis and/or fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array-CGH). We verified by bioinformatics and statistical approaches the occurrence of breakpoints in cytobands with or without OR genes. We found that OR genes are not involved in chromosome 11 reciprocal translocations, suggesting that different DNA motifs and mechanisms based on homology or non-homology recombination can cause chromosome 11 structural alterations. We also considered the proximity between the chromosomal territories of chromosome 11 and its partner chromosomes involved in the translocations by using the deposited Hi-C data concerning the possible occurrence of chromosome interactions. Interestingly, most of the breakpoints are located in regions highly involved in chromosome interactions. Further studies should be carried out to confirm the potential role of chromosome territories' proximity in promoting genome structural variation, so fundamental in our understanding of the molecular basis of medical genetics and evolutionary genetics.

Use of venetoclax in t(11;14) positive relapsed/refractory multiple myeloma: A systematic review.

BACKGROUND: The plasma cell malignancy, multiple myeloma (MM), remains incurable despite advanced treatment protocols. Overexpression of Bcl-2 (an anti-apoptotic protein), in MM harboring the translocation (11;14), contributes to resistance to prior therapy. Venetoclax, a selective oral inhibitor of BCL-2 is a novel agent that shows promise as a therapeutic agent. AIMS: The objective of this systematic review is to address how the use of venetoclax, alone or as a combination regimen, contributed to the treatment of patients with t(11:14) positive relapsed/refractory multiple myeloma (RRMM). DATA SOURCES: This systematic review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was done on 5th June 2022. A literature search was conducted on PubMed and Scopus, 145 articles were screened and 10 studies were included. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. DATA SUMMARY: Across the studies reviewed, a total of 311 patients were identified with t(11;14) positive RRMM. The overall response rate achieved ranged between 33% and 95.5%. Furthermore, the use of venetoclax has exhibited a favorable adverse effect profile. Side effects included hematological side effects, nausea, vomiting, and diarrhea. CONCLUSION: Venetoclax demonstrates promising results. When given with drugs like dexamethasone, daratumumab and carfilzomib, a synergistic effect is seen in treating translocation (11:14) positive relapsed/refractory MM. The use of venetoclax in clinical practice can potentially improve outcomes and quality of life in RRMM patients, and future research should continue to explore this promising treatment option.

Complex Chromosomal Rearrangement Involving Chromosomes 10 and 11, Accompanied by Two Adjacent 11p14.1p13 and 11p13p12 Deletions, Identified in a Patient with WAGR Syndrome.

Three years ago, our patient, at that time a 16-month-old boy, was discovered to have bilateral kidney lesions with a giant tumor in the right kidney. Chemotherapy and bilateral nephron-sparing surgery (NSS) for Wilms tumor with nephroblastomatosis was carried out. The patient also had eye affection, including glaucoma, eye enlargement, megalocornea, severe corneal swelling and opacity, complete aniridia, and nystagmus. The diagnosis of WAGR syndrome was suspected. De novo complex chromosomal rearrangement with balanced translocation t(10,11)(p15;p13) and a pericentric inversion inv(11)(p13q12), accompanied by two adjacent 11p14.1p13 and 11p13p12 deletions, were identified. Deletions are raised through the complex molecular mechanism of two subsequent rearrangements affecting chromosomes 11 and 10. WAGR syndrome diagnosis was clinically and molecularly confirmed, highlighting the necessity of comprehensive genetic testing in patients with congenital aniridia and/or WAGR syndrome.

Identification and validation of autophagy-related genes in primary open-angle glaucoma.

BACKGROUND: As the most common type of glaucoma, the etiology of primary open-angle glaucoma (POAG) has not been unified. Autophagy may affect the occurrence and development of POAG, while the specific mechanism and target need to be further explored. METHODS: The GSE27276 dataset from the Gene Expression Omnibus (GEO) database and the autophagy gene set from the GeneCards database were selected to screen differentially expressed autophagy-related genes (DEARGs) of POAG. Hub DEARGs were selected by constructing protein-protein interaction (PPI) networks and utilizing GSE138125 dataset. Subsequently, immune cell infiltration analysis, genome-wide association study (GWAS) analysis, gene set enrichment analysis (GSEA) and other analyses were performed on the hub genes. Eventually, animal experiments were performed to verify the mRNA levels of the hub genes by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: A total of 67 DEARGs and 2 hub DEARGs, HSPA8 and RPL15, were selected. The hub genes were closely related to the level of immune cell infiltration. GWAS analysis confirmed that the causative regions of the 2 hub genes in glaucoma were on chromosome 11 and chromosome 3, respectively. GSEA illustrated that pathways enriched for highly expressed HSPA8 and RPL15 contained immunity, autophagy, gene expression and energy metabolism-related pathways. qRT-PCR confirmed that the expression of Hspa8 and Rpl15 in the rat POAG model was consistent with the results of bioinformatics analysis. CONCLUSIONS: This study indicated that HSPA8 and RPL15 may affect the progression of POAG by regulating autophagy and provided new ideas for the pathogenesis and treatment of POAG.

Chromosomal fragile site breakage by EBV-encoded EBNA1 at clustered repeats.

Epstein-Barr virus (EBV) is an oncogenic herpesvirus associated with several cancers of lymphocytic and epithelial origin1-3. EBV encodes EBNA1, which binds to a cluster of 20 copies of an 18-base-pair palindromic sequence in the EBV genome4-6. EBNA1 also associates with host chromosomes at non-sequence-specific sites7, thereby enabling viral persistence. Here we show that the sequence-specific DNA-binding domain of EBNA1 binds to a cluster of tandemly repeated copies of an EBV-like, 18-base-pair imperfect palindromic sequence encompassing a region of about 21 kilobases at human chromosome 11q23. In situ visualization of the repetitive EBNA1-binding site reveals aberrant structures on mitotic chromosomes characteristic of inherently fragile DNA. We demonstrate that increasing levels of EBNA1 binding trigger dose-dependent breakage at 11q23, producing a fusogenic centromere-containing fragment and an acentric distal fragment, with both mis-segregated into micronuclei in the next cell cycles. In cells latently infected with EBV, elevating EBNA1 abundance by as little as twofold was sufficient to trigger breakage at 11q23. Examination of whole-genome sequencing of EBV-associated nasopharyngeal carcinomas revealed that structural variants are highly enriched on chromosome 11. Presence of EBV is also shown to be associated with an enrichment of chromosome 11 rearrangements across 2,439 tumours from 38 cancer types. Our results identify a previously unappreciated link between EBV and genomic instability, wherein EBNA1-induced breakage at 11q23 triggers acquisition of structural variations in chromosome 11.

Expanding the phenotypic spectrum of Chromosome 16p13.11 microduplication: A multicentric analysis of 206 patients.

INTRODUCTION: Recurrent chromosome 16p13.11 microduplication has been characterised in the literature as a cause of developmental delay, learning difficulties and behavioural abnormalities. It is a neurosusceptibility locus and has incomplete penetrance and variable expression. Other clinical features, such as cardiac abnormalities have also been reported. The duplicated region contains the MYH11 gene, which encodes the protein myosin-11 and is a component of the myosin heavy chain in smooth muscle. Recent literature has suggested 16p13.11 microduplication as one of the possible risk factors for thoracic aortic aneurysms and dissection (TAAD). Therefore, we studied the detailed phenotype of cases of chromosome 16p13.11 microduplication from seven centres in the United Kingdom (UK) to expand the phenotype, focusing on the cardiac abnormalities. METHODS: All individuals with a chromosome 16p13.11 microduplication seen in Clinical Genetics prior to June 2017 in 6 centres (prior to 2018 in the seventh centre) were identified through the regional genetics laboratory databases. A Microsoft Excel® proforma was created and clinical data was collected retrospectively from clinical genetics databases from the seven genetics services in the UK. The data was collated and analysed collectively. RESULTS: The majority of the individuals presented with (72%) developmental delay and (62%) behavioural abnormalities, in keeping with the published literature. 27% had some dysmorphic features, 14% had visual impairment and 8% had congenital cardiac abnormalities. Echocardiograms were performed in 50% of patients, and only 3.8% patients had aortic dilatation and no one had aortic dissection. 9.7% of patients were found to have a second genetic/chromosomal diagnosis, especially where there were additional phenotypic features. CONCLUSION: 16p13.11 microduplication is a neurosusceptibility locus and is associated with variable expression. It may be helpful to refer children with 16p13.11 microduplication for a cardiac review for congenital cardiac abnormalities and also for ophthalmological assessment. Further prospective studies with cardiac assessments are recommended in this cohort of patients to determine whether ongoing aortic surveillance is indicated. Guidelines about the frequency of surveillance are indicated, especially in individuals with normal cardiac findings. We also highlight the importance of considering a second diagnosis if the phenotype is inconsistent with that reported.

Chronic Lymphocytic Leukemia With Two B-Cell Populations of Discordant Light Chain Restrictions in Individual Patients: Parallel Development of Biclonal B-Cell Neoplasms or Clonal Evolution With Isotype Switch?

OBJECTIVES: To evaluate clinicopathologic characteristics of biclonal chronic lymphocytic leukemia (CLL). METHODS: Retrospectively analyze clinical data and pathologic features. RESULTS: Ten cases were identified in which flow cytometry demonstrated an abnormal B-cell population with a CLL-like immunophenotype but showed no definitive light chain restriction. All had cytogenetic abnormalities detected, including seven with two CLL-related abnormalities. Four of these showed features suggestive of clonal evolution, all having del(13q) as a "stem-line" abnormality and three showing del(11q) as a "side-line" abnormality. Five (50%) cases demonstrated deleterious NOTCH1 mutations, in contrast to 11.8% in a control group of monoclonal CLL (P < .05). Of the 10 patients, 5 received treatment, with good/partial response in three cases and therapeutic resistance in one case. The median treatment-free survival was estimated at 68 months. CONCLUSIONS: Despite a polytypic pattern of light chain expression, the neoplastic nature of biclonal CLL is suggested by a characteristic CLL phenotype and can be confirmed by cytogenetic and genomic analyses. The two clones with discordant light chain isotypes may share a "stem-line" cytogenetic abnormality, suggesting possible clonal evolution. Biclonal CLL is associated with NOTCH1 mutations, which may occur in a small subclone and gradually evolve in clonal size. Genomic analysis on light chain-sorted and/or chronologically collected samples may provide insight into clonal evolution in CLL.

Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study.

PURPOSE: We aimed to study prognostic factors and efficacy of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in first remission of patients with noninfant childhood acute lymphoblastic leukemia (ALL) with 11q23/KMT2A rearrangements treated with chemotherapy regimens between 1995 and 2010. PATIENTS AND METHODS: Data were retrospectively retrieved from 629 patients with 11q23/KMT2A-rearranged ALL from 17 members of the Ponte-di-Legno Childhood ALL Working Group. Clinical and biologic characteristics, early response assessed by minimal residual disease at the end of induction (EOI) therapy, and allo-HSCT were analyzed for their impact on outcomes. RESULTS: A specific 11q23/KMT2A translocation partner gene was identified in 84.3% of patients, with the most frequent translocations being t(4;11)(q21;q23) (n = 273; 51.5%), t(11;19)(q23;p13.3) (n = 106; 20.0%), t(9;11)(p21_22;q23) (n = 76; 14.3%), t(6;11)(q27;q23) (n = 20; 3.8%), and t(10;11)(p12;q23) (n = 14; 2.6%); 41 patients (7.7%) had less frequently identified translocation partner genes. Patient characteristics and early response varied among subgroups, indicating large biologic heterogeneity and diversity in therapy sensitivity among 11q23/KMT2A-rearranged ALL. The EOI remission rate was 93.2%, and the 5-year event-free survival (EFS) for the entire cohort was 69.1% ± 1.9%, with a range from 41.7% ± 17.3% for patients with t(9;11)-positive T-ALL (n = 9) and 64.8% ± 3.0% for patients with t(4;11)-positive B-ALL (n = 266) to 91.2% ± 4.9% for patients with t(11;19)-positive T-ALL (n = 34). Low EOI minimal residual disease was associated with favorable EFS, and induction failure was particularly predictive of nonresponse to further therapy and relapse and poor EFS. In addition, EFS was not improved by allo-HSCT compared with chemotherapy only in patients with both t(4;11)-positive B-ALL (n = 64 v 51; P = .10) and 11q23/KMT2A-rearranged T-ALL (n = 16 v 10; P = .69). CONCLUSION: Compared with historical data, prognosis of patients with noninfant 11q23/KMT2A-rearranged ALL has improved, but allo-HSCT failed to affect outcome. Targeted therapies are needed to reduce relapse and treatment-related mortality rates.

GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology.

Few genome-wide association studies (GWAS) analyzing genetic regulation of morphological traits of white blood cells have been reported. We carried out a GWAS of 12 morphological traits in 869 individuals from the general population of Sardinia, Italy. These traits, included measures of cell volume, conductivity and light scatter in four white-cell populations (eosinophils, lymphocytes, monocytes, neutrophils). This analysis yielded seven statistically significant signals, four of which were novel (four novel, PRG2, P2RX3, two of CDK6). Five signals were replicated in the independent INTERVAL cohort of 11 822 individuals. The most interesting signal with large effect size on eosinophil scatter (P-value = 8.33 x 10-32, beta = -1.651, se = 0.1351) falls within the innate immunity cluster on chromosome 11, and is located in the PRG2 gene. Computational analyses revealed that a rare, Sardinian-specific PRG2:p.Ser148Pro mutation modifies PRG2 amino acid contacts and protein dynamics in a manner that could possibly explain the changes observed in eosinophil morphology. Our discoveries shed light on genetics of morphological traits. For the first time, we describe such large effect size on eosinophils morphology that is relatively frequent in Sardinian population.

Clinical study of mature B-cell lymphoma in 11 children with chromosome 11 long-arm abnormalities / 中华血液学杂志

Objective: To explore the clinical, pathological, diagnostic, treatment, and prognostic features of children with mature B-cell lymphoma (MBCL) . Methods: This retrospective study included pediatric patients with MBCL with chromosome 11 long-arm abnormalities who were diagnosed and treated at our hospital from December 2018 to February 2023. Results: Among the 11 pediatric patients with MBCL, nine were male and two were female, with a median age of 9 (2-13) years and a median disease course of 1.8 (0.5-24) months. The clinical manifestations were cervical lymph node enlargement in four patients, nasal congestion and snoring in four patients, abdominal pain in two patients, and difficulty breathing in one patient. There were seven cases of Burkitt's lymphoma, two of follicular lymphoma, and two of advanced B-cell lymphoma according to the pathological morphology examination. No patients had central nervous system or bone marrow involvement, and no extensive metastasis was observed on B-ultrasound or positron emission tomography-computed tomography (PET/CT). One patient had a huge tumor lesion. The Revised International Pediatric Non-Hodgkin Lymphoma Staging System classified four patients as stage Ⅱ, five as stage Ⅲ, and two as stage Ⅳ. 11q probe detection showed five cases of 11q gain, three of 11q loss, and three of both gain and loss. FISH showed positive MYC expression in three patients, including eight with advanced B-cell lymphoma with 11q abnormalities and three with Burkitt's lymphoma with 11q abnormalities. According to the 2019 edition of the National Health Commission's diagnostic and treatment guidelines for invasive MBCL in children, one patient was classified as Group A, two as Group B, and eight as Group C. Early evaluation of the efficacy showed complete remission. After mid-term evaluation, the intensity of chemotherapy was reduced in Group B and Group C. Among two cases of chemotherapy, the remaining nine cases had a median follow-up of 32 (6-45) months, and none had event-related survival. Conclusion: The incidence of MBCL with 11q abnormalities in children is low, clinical symptoms are mild, and progression is slow. The absence of MYC, BCL2, BCL6 rearrangements, C-MYC negative and 11q abnormalities on FISH is an important diagnostic indicator, and reducing the intensity of chemotherapy can improve prognosis.

[Clinical study of mature B-cell lymphoma in 11 children with chromosome 11 long-arm abnormalities].

Objective: To explore the clinical, pathological, diagnostic, treatment, and prognostic features of children with mature B-cell lymphoma (MBCL) . Methods: This retrospective study included pediatric patients with MBCL with chromosome 11 long-arm abnormalities who were diagnosed and treated at our hospital from December 2018 to February 2023. Results: Among the 11 pediatric patients with MBCL, nine were male and two were female, with a median age of 9 (2-13) years and a median disease course of 1.8 (0.5-24) months. The clinical manifestations were cervical lymph node enlargement in four patients, nasal congestion and snoring in four patients, abdominal pain in two patients, and difficulty breathing in one patient. There were seven cases of Burkitt's lymphoma, two of follicular lymphoma, and two of advanced B-cell lymphoma according to the pathological morphology examination. No patients had central nervous system or bone marrow involvement, and no extensive metastasis was observed on B-ultrasound or positron emission tomography-computed tomography (PET/CT). One patient had a huge tumor lesion. The Revised International Pediatric Non-Hodgkin Lymphoma Staging System classified four patients as stage Ⅱ, five as stage Ⅲ, and two as stage Ⅳ. 11q probe detection showed five cases of 11q gain, three of 11q loss, and three of both gain and loss. FISH showed positive MYC expression in three patients, including eight with advanced B-cell lymphoma with 11q abnormalities and three with Burkitt's lymphoma with 11q abnormalities. According to the 2019 edition of the National Health Commission's diagnostic and treatment guidelines for invasive MBCL in children, one patient was classified as Group A, two as Group B, and eight as Group C. Early evaluation of the efficacy showed complete remission. After mid-term evaluation, the intensity of chemotherapy was reduced in Group B and Group C. Among two cases of chemotherapy, the remaining nine cases had a median follow-up of 32 (6-45) months, and none had event-related survival. Conclusion: The incidence of MBCL with 11q abnormalities in children is low, clinical symptoms are mild, and progression is slow. The absence of MYC, BCL2, BCL6 rearrangements, C-MYC negative and 11q abnormalities on FISH is an important diagnostic indicator, and reducing the intensity of chemotherapy can improve prognosis.

Bioinformatics analysis of miRNAs in the neuroblastoma 11q-deleted region reveals a role of miR-548l in both 11q-deleted and MYCN amplified tumour cells.

Neuroblastoma is a childhood tumour that is responsible for approximately 15% of all childhood cancer deaths. Neuroblastoma tumours with amplification of the oncogene MYCN are aggressive, however, another aggressive subgroup without MYCN amplification also exists; rather, they have a deleted region at chromosome arm 11q. Twenty-six miRNAs are located within the breakpoint region of chromosome 11q and have been checked for a possible involvement in development of neuroblastoma due to the genomic alteration. Target genes of these miRNAs are involved in pathways associated with cancer, including proliferation, apoptosis and DNA repair. We could show that miR-548l found within the 11q region is downregulated in neuroblastoma cell lines with 11q deletion or MYCN amplification. In addition, we showed that the restoration of miR-548l level in a neuroblastoma cell line led to a decreased proliferation of these cells as well as a decrease in the percentage of cells in the S phase. We also found that miR-548l overexpression suppressed cell viability and promoted apoptosis, while miR-548l knockdown promoted cell viability and inhibited apoptosis in neuroblastoma cells. Our results indicate that 11q-deleted neuroblastoma and MYCN amplified neuroblastoma coalesce by downregulating miR-548l.

Further understanding of paternal uniparental disomy in Beckwith-Wiedemann syndrome.

INTRODUCTION: Paternal uniparental disomy of chromosome 11 (upd(11)pat) accounts for up to 20% of molecularly confirmed Beckwith-Wiedemann spectrum (BWSp) cases. It belongs to the BWSp subgroup with the second highest tumor risk, and therefore needs particular awareness in research, diagnostics and clinical management. AREAS COVERED: We overview the contribution of paternal (mosaic) uniparental disomy of chromosome 11 (UPD, upd(11)pat) and mosaic paternal uniparental diploidy in patients with Beckwith-Wiedemann features. The review comprises the current knowledge on their formation and their molecular and clinical consequences. Accordingly, the consequences for diagnostic testing and clinical monitoring are compiled. EXPERT OPINION: The necessity to diagnostically identify and thus discriminate genome-wide paternal uniparental disomy, and upd(11)pat becomes obvious, due to the differences in the clinical course, disease prognosis, and treatment. In particular, monitoring of tumor development by liquid biopsy might be a promising option in the future. From the research point of view, it should be addressed why 11p is prone to mitotic recombination and thus also provide to the role of upd(11) as second hit in tumorigenesis.

Enhancing DLG2 Implications in Neuropsychiatric Disorders: Analysis of a Cohort of Eight Patients with 11q14.1 Imbalances.

Neurodevelopmental disorders (NDDs) are considered synaptopathies, as they are due to anomalies in neuronal connectivity during development. DLG2 is a gene involved insynaptic function; the phenotypic effect of itsalterations in NDDs has been underestimated since few cases have been thoroughly described.We report on eight patients with 11q14.1 imbalances involving DLG2, underlining its potential effects on clinical presentation and its contribution to NDD comorbidity by accurate neuropsychiatric data collection. DLG2 is a very large gene in 11q14.1, extending over 2.172 Mb, with alternative splicing that gives rise to numerous isoforms differentially expressed in brain tissues. A thorough bioinformatic analysis of the altered transcripts was conducted for each patient. The different expression profiles of the isoforms of this gene and their influence on the excitatory-inhibitory balance in crucial brain structures could contribute to the phenotypic variability related to DLG2 alterations. Further studies on patients would be helpful to enrich clinical and neurodevelopmental findings and elucidate the molecular mechanisms subtended to NDDs.