CRISPRi screen of long non-coding RNAs identifies LINC03045 regulating glioblastoma invasion.

INTRODUCTION: Glioblastoma (GBM) invasion studies have focused on coding genes, while few studies evaluate long non-coding RNAs (lncRNAs), transcripts without protein-coding potential, for role in GBM invasion. We leveraged CRISPR-interference (CRISPRi) to evaluate invasive function of GBM-associated lncRNAs in an unbiased functional screen, characterizing and exploring the mechanism of identified candidates. METHODS: We implemented a CRISPRi lncRNA loss-of-function screen evaluating association of lncRNA knockdown (KD) with invasion capacity in Matrigel. Top screen candidates were validated using CRISPRi and oligonucleotide(ASO)-mediated knockdown in three tumor lines. Clinical relevance of candidates was assessed via The Cancer Genome Atlas(TCGA) and Genotype-Tissue Expression(GTEx) survival analysis. Mediators of lncRNA effect were identified via differential expression analysis following lncRNA KD and assessed for tumor invasion using knockdown and rescue experiments. RESULTS: Forty-eight lncRNAs were significantly associated with 33-83% decrease in invasion (p<0.01) upon knockdown. The top candidate, LINC03045, identified from effect size and p-value, demonstrated 82.7% decrease in tumor cell invasion upon knockdown, while LINC03045 expression was significantly associated with patient survival and tumor grade(p<0.0001). RNAseq analysis of LINC03045 knockdown revealed that WASF3, previously implicated in tumor invasion studies, was highly correlated with lncRNA expression, while WASF3 KD was associated with significant decrease in invasion. Finally, WASF3 overexpression demonstrated rescue of invasive function lost with LINC03045 KD. CONCLUSION: CRISPRi screening identified LINC03045, a previously unannotated lncRNA, as critical to GBM invasion. Gene expression is significantly associated with tumor grade and survival. RNA-seq and mechanistic studies suggest that this novel lncRNA may regulate invasion via WASF3.

Mortality following mechanical thrombectomy for ischemic stroke in patients with COVID-19.

OBJECTIVES: Multiple prior studies have shown a relationship between COVID-19 and strokes; further, COVID-19 has been shown to influence both time-to-thrombectomy and overall thrombectomy rates. Using large-scale, recently released national data, we assessed the association between COVID-19 diagnosis and patient outcomes following mechanical thrombectomy. MATERIALS AND METHODS: Patients in this study were identified from the 2020 National Inpatient Sample. All patients with arterial strokes undergoing mechanical thrombectomy were identified using ICD-10 coding criteria. Patients were further stratified by COVID diagnosis (positive vs. negative). Other covariates, including patient/hospital demographics, disease severity, and comorbidities were collected. Multivariable analysis was used to determine the independent effect of COVID-19 on in-hospital mortality and unfavorable discharge. RESULTS: 5078 patients were identified in this study; 166 (3.3%) were COVID-19 positive. COVID-19 patients had a significantly higher mortality rate (30.1% vs. 12.4%, p < 0.001). When controlling for patient/hospital characteristics, APR-DRG disease severity, and Elixhauser Comorbidity Index, COVID-19 was an independent predictor of increased mortality (OR 1.13, p = 0.002). COVID-19 was not significantly related to discharge disposition (p = 0.480). Older age and increased APR-DRG disease severity were also correlated with increase morality. CONCLUSIONS: Overall, this study indicates that COVID-19 is a predictor of mortality among mechanical thrombectomy. This finding is likely multifactorial but may be related to multisystem inflammation, hypercoagulability, and re-occlusion seen in COVID-19 patients. Further research would be needed to clarify these relationships.

Development of multifocal glioblastoma after radiotherapy for craniopharyngioma: illustrative case.

BACKGROUND: Radiation-induced glioblastoma (GBM) in patients previously treated for craniopharyngioma is a rare phenomenon. To the authors' knowledge, only seven cases have previously been documented in the literature. OBSERVATIONS: Herein, the authors report a case of a patient presenting with a new diagnosis of multifocal GBM 15 years after having received adjuvant radiotherapy for a craniopharyngioma. Magnetic resonance imaging revealed an extensive enhancing infiltrative lesion in the right frontal lobe as well as two satellite lesions in the contralateral frontal lobe. Histopathology on biopsy was consistent with GBM. LESSONS: Even though this case is rare, it is nevertheless important to recognize GBM as a potential side effect of radiation. Long-term follow-up in postradiation craniopharyngioma patients is crucial for early detection.

Increased time to surgery and worse perioperative outcome in benign brain tumor patients with COVID-19.

BACKGROUND: The COVID-19 pandemic caused significant disruptions to healthcare systems around the world, due to both high resource utilization and concern for disease spread. Delays in non-emergent surgeries have also affected chronic disease management, including that of benign brain tumors such as meningiomas and pituitary adenomas. To evaluate the effect of COVID-19 infection on benign brain tumor resection rates and subsequent perioperative and inpatient outcomes, this study utilized the 2020 National Inpatient Sample (NIS) to investigate rates of surgical resection, time to surgery, and mortality among benign brain tumor patients with and without COVID-19. METHODS: Patient data from April 2020 to December 2020 was extracted from the NIS. Confirmed COVID-19 diagnosis was identified using the ICD-10 diagnosis code U07.1. Patients with benign neoplasms of the cerebral meninges, cranial nerves, pituitary gland, craniopharyngeal duct, and brain were included in the study. Patient socio-demographics, hospital characteristics, and clinical comorbidities were obtained. Outcome variables included rates of surgical resection, time to surgery, in-hospital mortality, length of stay, and discharge disposition. RESULTS: The study analysis consisted of 13,053 patients with benign intracranial neoplasms who met inclusion criteria; 597 (4.6%) patients were COVID-19 positive. Patients with COVID-19 were more likely to be older and male than COVID-19 negative patients. Patients with COVID-19 had increased overall likelihood of mortality (OR 2.36, 95% CI 1.72-3.25, p < 0.0001). Even when controlling for sociodemographic/hospital factors and comorbidities, COVID-19 positive patients had a significantly longer time to surgery (8.7 days vs. 0.9 days, p < 0.0001) than COVID negative patients, and were associated with a decreased likelihood of undergoing surgery on index admission overall (OR 0.17, 95% CI 0.10-0.29, p < 0.0001). CONCLUSIONS: As expected, COVID-19 infection was associated with worse inpatient outcomes in effectively all measured categories, including longer time to surgery, decreased likelihood of receiving surgery on index admission, and increased likelihood of in-hospital mortality. These findings emphasize the effect that COVID-19 has on other aspects of patient care and highlight the importance of appropriate avenues of care for patients who are COVID-19 positive. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome for these patients is essential in efficient triage and optimizing treatment for these patients in the future. Further study is needed to elucidate causal relationships on the outcomes of benign brain tumor patients.

The effect of COVID-19 on treatment and outcomes following ischemic stroke: A national assessment.

INTRODUCTION: COVID-19 has had innumerable impacts on the healthcare system, both by worsening patient illness and impeding effective and efficient care. Further, COVID-19 has been tied to increased rates of ischemic stroke, particularly among young patients. We utilized a national database to assess associations of COVID-19 with thrombectomy rates, mortality, and discharge disposition among stroke patients. METHODS: Patients were identified from the National Inpatient Sample (NIS, 2020). Inclusion criteria selected for adult ischemic stroke patients; those with venous thrombosis or unspecified cerebral infarction were excluded. Patients were stratified by presence or absence of COVID-19 diagnosis. Outcome variables included mechanical thrombectomy, in-hospital mortality, and discharge disposition. Additional patient demographics, hospital characteristics, and disease severity metrics were collected. Statistical analysis was performed via multivariable logistic regression and log-binary regression. RESULTS: 54,368 patients were included in the study; 2116 (3.89%) were diagnosed with COVID-19. COVID-19 was associated with lower rates of mechanical thrombectomy (OR 0.94, p < 0.0001), higher rates of in-hospital mortality (OR 1.14, p < 0.0001), and unfavorable discharge disposition (OR 1.08, p < 0.0001), even when controlling for illness severity. Other relationships, such as a male predominance among stroke patients with COVID-19, were also identified. CONCLUSION: This study identified a relationship between COVID-19 diagnosis and worse outcomes for each metric assessed, including mechanical thrombectomy rates, in-hospital mortality, and discharge disposition. Several factors might underly this, ranging from systemic/multisystem inflammation and worsened disease severity to logistical barriers to treatment caused by COVID-19. Further research is needed to determine causality of these findings.

Coronavirus disease-19 is associated with decreased treatment access and worsened outcomes in malignant brain tumor patients.

Background: The global coronavirus disease-19 (COVID-19) pandemic has resulted in procedural delays around the world; however, timely and aggressive surgical resection for malignant brain tumor patients is essential for outcome optimization. To investigate the association between COVID-19 and outcomes of these patients, we queried the 2020 National Inpatient Sample (NIS) for differences in rates of surgical resection, time to surgery, mortality, and discharge disposition between patients with and without confirmed COVID-19 infection. Methods: Patient data were taken from the NIS from April 2020 to December 2020. COVID-19 diagnosis was determined with the International Classification of Diseases, Tenth Revision, Clinical Modification code U07.1. Results: A total of 30,671 malignant brain tumor patients met inclusion criteria and 738 (2.4%) patients had a confirmed COVID-19 diagnosis. COVID-19-positive patients had lower likelihood of receiving surgery (Odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63, P < 0.0001), increased likelihood of mortality (OR 2.18, 95% CI 1.78-2.66, P < 0.0001), and increased likelihood of non-routine discharge (OR 1.25, 95% CI 1.13-1.39, P < 0.0001). Notably, COVID patients receiving surgery were not associated with surgical delay (P = 0.17). Conclusion: COVID-19 infection was associated with worse patient outcome in malignant brain tumor patients, including decreased likelihood of receiving surgery, increased likelihood of mortality, and increased likelihood of non-routine discharge. Our study highlights the need to balance the risks and benefits of delaying surgery for malignant brain tumor patients with COVID-19. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome provides important insight in effective triage for these patients in the situations where resources are limited.

Association of carotid endarterectomy at low-volume centers with higher likelihood of major complications and nonroutine discharge.

OBJECTIVE: Carotid artery stenosis (CAS) is associated with an annual stroke risk of 2%-5%, and revascularization with carotid endarterectomy (CEA) can reduce this risk. While studies have demonstrated that hospital CEA volume is associated with mortality and myocardial infarction, CEA volume cutoffs in studies are relatively arbitrary, and no specific analyses on broad complications and discharge disposition have been performed. In this study, the authors systematically set out to identify a cutoff at which CEA procedural volume was significantly associated with major complications and nonroutine discharge. METHODS: Asymptomatic and symptomatic CAS patients undergoing CEA were retrospectively identified in the Nationwide Readmissions Database (2010-2018). The association of CEA volume with outcomes was explored as a continuous variable using locally estimated scatterplot smoothing. The identified volume cutoff was used to generate dichotomous volume cohorts, and multivariate analyses of patient and hospital characteristics were conducted to evaluate the association of CEA volume with major complications and discharge disposition. RESULTS: Between 2010 and 2018, 308,933 asymptomatic and 32,877 symptomatic patients underwent CEA. Analysis of CEA volume with outcomes as a continuous variable demonstrated that an increase in volume was associated with a lower risk until a volume of approximately 7 cases per year (20th percentile). A total of 6702 (2.2%) asymptomatic and 1040 (3.2%) symptomatic patients were treated at the bottom 20% of hospital procedure volume. Increased rates of complications were seen at low-volume centers among asymptomatic (3.66% vs 2.77%) and symptomatic (7.4% vs 6.87%) patients. Asymptomatic patients treated at low-volume centers had an increased likelihood of major complications (OR 1.26, 95% CI 1.07-1.49; p = 0.007) and nonroutine discharge (OR 1.36, 95% CI 1.24-1.50; p < 0.0001). Symptomatic patients treated at low-volume centers were also more likely to experience major complications (OR 1.47, 95% CI 1.07-2.02; p = 0.02) and nonroutine discharge (OR 1.26, 95% CI 1.07-1.47; p = 0.005). Mortality rates were similar between low- and high-volume hospitals among asymptomatic (0.36% and 0.32%, respectively) and symptomatic (1.06% and 1.49%, respectively) patients, while volume was not significantly associated with mortality among asymptomatic (OR 1.06, 95% CI 0.67-1.65; p = 0.81) and symptomatic (OR 0.81, 95% CI 0.43-1.54; p = 0.52) patients in multivariate analysis. CONCLUSIONS: CEA patients, asymptomatic or symptomatic, are at a higher risk of major complications and nonroutine discharge at low-volume centers. Analysis of CEA as a continuous variable demonstrated a cutoff at 7 cases per year, and further study may identify factors associated with improved outcome at the lowest-volume centers.

Carotid artery stenting for asymptomatic stenosis is associated with decreased 30-day readmission at very high volume centers.

Endovascular carotid artery stenting (CAS) is a common treatment for carotid artery stenosis and stroke prevention. Previous studies have shown that high procedural volume centers are associated with improved patient outcomes. Unplanned 30-day readmissions, which are associated with significant expenses, are increasingly used as a metric of patient outcome. Despite prior studies evaluating associations between procedural volume and multiple outcomes, the association between very high CAS volume and short-term (30-day) readmission has not yet been evaluated in a large multicenter study. The National Readmissions Database (NRD) was analyzed retrospectively from 2010 to 2015 to evaluate the association between hospital procedural volume and patient outcomes in asymptomatic and symptomatic CAS patients. Very high volume centers (VHVC) were defined as the top 10% hospitals in terms of procedural volume, performing >= 79 procedures a year. Univariate and multivariate analyses of patient and hospital characteristics evaluated associations with short-term (30-day) readmissions (SR), long-term (90-day) readmissions (LR), index mortality, discharge disposition, major complications, and neurological complications. A total of 36,128 asymptomatic patients and 8,390 symptomatic patients who underwent CAS were identified. Asymptomatic CAS patients treated at VHVCs were associated with decreased likelihood of SR (OR 0.88, 95% CI 0.80-0.95, p = 0.003) and LR (OR 0.91, 95% CI 0.85-0.99, p = 0.037) compared to asymptomatic patients at non-VHVCs. There was no significant difference in SR or LR between symptomatic CAS patients treated at a VHVC vs. non-VHVC. Our findings provide additional evidence to support the role of experience in improved CAS treatment outcomes.

Pediatric patients with malignant brain tumor treated at children's hospitals: association with fewer unplanned readmissions.

OBJECTIVE: Pediatric primary brain tumors are the leading cause of death among childhood cancers. Guidelines recommend specialized care with a multidisciplinary team and focused treatment protocols to optimize outcomes in this patient population. Furthermore, readmission is a key metric of patient outcomes and has been used to inform reimbursement. However, no prior study has analyzed national database-level records to evaluate the role of care in a designated children's hospital following pediatric tumor resection and its impact on readmission rates. The goal of this study was to investigate whether treatment at a children's hospital rather than a nonchildren's hospital has a significant effect on outcome. METHODS: The Nationwide Readmissions Database records from 2010 to 2018 were analyzed retrospectively to evaluate the effect of hospital designation on patient outcomes after craniotomy for brain tumor resection, and results are reported as national estimates. Univariate and multivariate regression analyses of patient and hospital characteristics were conducted to evaluate if craniotomy for tumor resection at a designated children's hospital was independently associated with 30-day readmissions, mortality rate, and length of stay. RESULTS: A total of 4003 patients who underwent craniotomy for tumor resection were identified using the Nationwide Readmissions Database, with 1258 of these cases (31.4%) treated at children's hospitals. Patients treated at children's hospitals were associated with decreased likelihood of 30-day hospital readmission (OR 0.68, 95% CI 0.48-0.97, p = 0.036) compared to patients treated at nonchildren's hospitals. There was no significant difference in index mortality between patients treated at children's hospitals and those treated at nonchildren's hospitals. CONCLUSIONS: The authors found that patients undergoing craniotomy for tumor resection at children's hospitals were associated with decreased rates of 30-day readmission, with no significant difference in index mortality. Future prospective studies may be warranted to confirm this association and identify components contributing to improved outcomes in care at children's hospitals.

Myelomeningocele repair at pediatric hospitals: association with routine discharge and shorter hospital stay.

OBJECTIVE: Postnatal repair for myelomeningocele (MMC) is a time-sensitive and technically challenging procedure. More experienced hospitals may provide improved outcomes for the complexity of care associated with these patients. No prior study has investigated the impact of MMC treatment at pediatric hospitals. The authors sought to examine the effect of pediatric hospital designation on patients undergoing postnatal MMC repair to identify factors associated with maximizing improved patient outcomes. METHODS: The Nationwide Readmissions Database records from 2010 to 2018 were analyzed retrospectively to determine the effect of hospital designation on patient outcomes after postnatal MMC repair. Univariate and multivariate regression analyses of patient and hospital characteristics were conducted to evaluate if MMC repair at a designated pediatric hospital was independently associated with patient outcomes of perinatal infection rates, discharge disposition, and length of stay. RESULTS: Of the total of 6353 pediatric patients who underwent postnatal MMC repair between 2010 and 2018, 2224 (35.0%) received care at a pediatric hospital. Those with an extreme level of disease burden as defined by the all patient refined diagnosis-related group severity of illness index were more likely to be treated at a pediatric hospital (p = 0.03). Patients undergoing repair at a pediatric hospital were also associated with a decreased likelihood of perinatal infection (OR 0.54, 95% CI 0.35-0.83, p = 0.005); greater likelihood of routine disposition (OR 4.85, 95% CI 2.34-10.06, p < 0.0001); and shorter length of stay (incidence rate ratio 0.88, 95% CI 0.77-0.995, p = 0.04). CONCLUSIONS: Pediatric patients requiring intervention for postnatal repair of MMC may benefit from the multidisciplinary subspeciality care offered at pediatric hospitals. The authors found that postnatal repair of MMC at pediatric hospitals was associated with a greater likelihood of improved patient outcomes.

Modulating glioblastoma chemotherapy response: Evaluating long non-coding RNA effects on DNA damage response, glioma stem cell function, and hypoxic processes.

Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor, with an estimated annual incidence of 17 000 new cases in the United States. Current treatments for GBM include chemotherapy, surgical resection, radiation therapy, and antiangiogenic therapy. However, despite the various therapeutic options, the 5-year survival rate remains at a dismal 5%. Temozolomide (TMZ) is the first-line chemotherapy drug for GBM; however, poor TMZ response is one of the main contributors to the dismal prognosis. Long non-coding RNAs (lncRNAs) are nonprotein coding transcripts greater than 200 nucleotides that have been implicated to mediate various GBM pathologies, including chemoresistance. In this review, we aim to frame the TMZ response in GBM via exploration of the lncRNAs mediating three major mechanisms of TMZ resistance: (1) regulation of the DNA damage response, (2) maintenance of glioma stem cell identity, and (3) exploitation of hypoxia-associated responses.

Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment.

Glioblastoma (GBM) is the most common primary brain tumor, carrying a very poor prognosis, with median overall survival at about 12 to 15 months despite surgical resection, chemotherapy with temozolomide (TMZ), and radiation therapy. GBM recurs in the vast majority of patients, with recurrent tumors commonly displaying increase in resistance to standard of care chemotherapy, TMZ, as well as radiotherapy. One of the most commonly cited mechanisms of chemotherapeutic and radio-resistance occurs via the glucose-regulated protein 78 (GRP78), a well-studied mediator of the unfolded protein response (UPR), that has also demonstrated potential as a biomarker in GBM. Overexpression of GRP78 has been directly correlated with malignant tumor characteristics, including higher tumor grade, cellular proliferation, migration, invasion, poorer responses to TMZ and radiation therapy, and poorer patient outcomes. GRP78 expression is also higher in GBM tumor cells upon recurrence. Meanwhile, knockdown or suppression of GRP78 has been shown to sensitize cells to TMZ and radiation therapy. In light of these findings, various novel developing therapies are targeting GRP78 as monotherapies, combination therapies that enhance the effects of TMZ and radiation therapy, and as treatment delivery modalities. In this review, we delineate the mechanisms by which GRP78 has been noted to specifically modulate glioblastoma behavior and discuss current developing therapies involving GRP78 in GBM. While further research is necessary to translate these developing therapies into clinical settings, GRP78-based therapies hold promise in improving current standard-of-care GBM therapy and may ultimately lead to improved patient outcomes.

MECOM: A Very Interesting Gene Involved also in Lymphoid Malignancies.

OBJECTIVES: The Ecotropic Viral Integration Site 1 gene (EVI1), also known as the MDS1 and EVI1 Complex Locus (MECOM), is located on chromosome 3q26.2. Extensive studies have implicated this gene's role in maintaining and replicating normal hematopoietic stem cells, as well as its role as an oncogene when aberrantly expressed. Translocations involving the MECOM gene at 3q26.2 are well-documented and characterized in myeloid disorders, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myelogenous leukemia (CML), and is associated with a poor prognosis. Recently, cases of MECOM rearrangements and activation have also been documented in lymphoid malignancies, including acute lymphoblastic leukemia (ALL) and persistent polyclonal binucleated B-cell lymphoma (PBBL). A review of the literature reveals four confirmed cases of MECOM cytogenetic abnormalities in lymphoid disorders, each of which could potentially implicate MECOM in the development or transformation of lymphoid disease. In two cases, a B-cell ALL (B-ALL) case and a T-cell non-Hodgkin's lymphoma case, the MECOM aberration was the sole abnormality, suggesting that it may have an important role in the development of the disease. In the other two cases, a case of 5q- syndrome and a case of plasma cell myeloma, both acquired a MECOM aberration as the cases transformed to ALL, potentially implying that it has a role in ALL disease transformation. There were also 82 cases of PBBL with inv(3) in particular as the MECOM abnormality of interest. In the literature, there were also mentions of at least 38 other cases of MECOM aberrant activation, but these cases may or may not involve 3q26.2 rearrangement. MECOM overexpression may also develop independently of any chromosomal rearrangement, with other possible pathways involved. A query of the Mitelman Database of Chromosomal Aberrations and Gene Fusions in Cancer revealed another 12 cases where 3q26 rearrangements were reported in lymphoid malignancies, but none of these studies performed fluorescence in-situ hybridization (FISH) to confirm or deny the presence of a MECOM rearrangement. Recent findings also demonstrate that MECOM may also play an important role in lymphoid leukemogenesis, progression, and transformation, although it may be in a manner distinct from that in myeloid malignancies. Overall, MECOM still needs to be further characterized and investigated in the context of lymphoid malignancies as a potential biomarker and therapeutic target.

A t(3;8)(q26.2;q24) involving the EVI1 (MECOM) Gene.

OBJECTIVES: Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) primarily characterized by increased red blood cell production. We report a case of a 68-year-old male with a history of PV. About four years later, the patient developed myelofibrosis. A bone marrow biopsy confirmed the presence of myelofibrosis confirmed by a hypercellular bone marrow (80%) with increased reticulin fibrosis (MF2-3), 5% blasts, and a normal 46,XY karyotype. A follow-up bone marrow biopsy documented acute myeloid leukemia (post-polycythemic myelofibrosis with acute leukemic transformation) with 20-30% blasts in the bone marrow. Chromosome analysis revealed an abnormal male karyotype with a t(3;8)(q26.2;q23) involving MECOM (EVI1) on 11q23 and confirmed by FISH and no PVTI rearrangement. To the best of our knowledge, this translocation has not been reported in acute myeloid leukemia (AML), de novo or therapy related-myelodysplastic syndrome (MDS), or MDS or myeloproliferative disorder progressing to AML. However, further studies need to be conducted to elucidate and identify the roles of genes other than MECOM involved in this peculiar translocation with such a poor prognosis.

A Plasma Cell Myeloma Case with an Abnormal Clone with a t(8;22)(q24.1;q11.2) Within the Context of a Hyperdiploid Complex Karyotype.

OBJECTIVES: We report here a 74-year-old male who was seen for recurrent respiratory infections, fatigue, and weight loss in November 2016. Bone marrow biopsy showed 90% involvement by plasma cell myeloma (PCM) [90% plasma cells, 40% cellular bone marrow]. Cytogenetic analysis of the bone marrow showed a complex karyotype described as: 53,Y,add(X)(p22.1),del(1)(p13p22),+3,add(3)(p13),add(4)(p12),+6,del(6)(q13q25),t(8;22)(q24.1;q11.2),+9,+11,+15,+15,+21[7]/46,XY[13]. This particular pattern with deletion 1p, deletion 6q, and a t(8;22)(q24;q11.2) within the context of a complex karyotype is seen in PCM. Fluorescence in situ hybridization analysis on the CDC138 sample was positive for additional copies of CEP7 (centromere 7), CEP9 (centromere 9), CEP11 (centromere 11), and CEP15 (centromere 15), suggesting polysomy. FISH using the MYC Vysis break apart probe showed evidence of MYC rearrangement similar to the breakpoint site seen in Burkitt lymphoma with t(8;22)(q24;q11). FISH using the IGL break apart probe (Cytocell, Cambridge, UK) showed evidence of a 22q11.2 rearrangement. The signal pattern showed a residual green signal (BCR), a green signal on the derivative 8, and a red signal on the derivative 22, suggesting that the breakpoint at 22q11.2 in this patient was located downstream of the BCR region of the IGL gene. The variant Burkitt-type translocation, t(8;22)(q24;q11), is a very rare abnormality in PCM, and this case is one of only several reported to date. In these patients, MYC abnormalities appear late in the course of the disease and have an immature phenotype. A review of several cases in the literature suggests that this translocation leads the MYC gene under direct regulation of the enhancer of the partner gene, and in our case, the IGL or a nearby gene, thereby causing high level transcription of MYC. This abnormality is usually present within a complex karyotype and is associated with tumor progression and a poor prognosis.

The t(12;21)(p13;q22) in Pediatric B-Acute Lymphoblastic Leukemia: An Update.

Erratum: Figure 1 on the last edition The Journal of the Association of Genetic Technologists. 2017;43(3): 113-127 does not contain the derivative 21. We are replacing this figure with the present one. In the section Secondary genetic aberrations we would like to add that: Deletions of 11q23 are observed in 5-6% of cases (Raynaud et al., 1999; Attarbaschi et al., 2004; Alvarez et al., 2005; Forestier et al., 2007).

The t(12;21)(p13;q22) in Pediatric B-Acute Lymphoblastic Leukemia: An Update.

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is the most common hematological malignancy in children, and the t(12;21)(p13;q22) occurs in approximately 25% of these cases, making it is the most prevalent chromosomal abnormality. The t(12;21) which disrupts hematopoietic differentiation and proliferation, and can be present as a sole abnormality or within the context of a complex karyotype characterized by three or more chromosomal abnormalities. The prognosis of t(12;21) within a complex karyotype is extensively debated. In this review, we discuss the literature regarding t(12;21) and summarize the cytogenetic features found in 363 pediatric cases compiled from the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer. Cytogenetically, most of the cases had secondary chromosomal abnormalities, about half of which were in the context of a complex karyotype. Trisomy 21 was found to be the most common numerical abnormality in almost one-fifth of the cases, and deletions on chromosome 12 and 6 occurred in 16.9% and 12.5% of cases, respectively. In general, t(12;21) in B-ALL is associated with a favorable prognosis. Herein, we found no significant difference in survival outcome of t(12;21) with a on-complex or complex karyotype.