Astrocytoma with high-grade features and MYBL1-MMP16 fusion.

Background: Gliomas represent the most common primary intraparenchymal brain tumors in adult and pediatric patients. Neuropathological work-up of these gliomas typically entails the determination of isocitrate dehydrogenase (IDH) mutational status, presence or absence of 1p/19q co-deletion, and O6 methylguanine-DNA methyl-transferase (MGMT) promoter methylation status. Case Description: We present here an unusual case of a posterior fossa tumor in a 51-year-old female, which was initially diagnosed as astrocytoma with some high-grade features that recurred, displaying even more aggressive features such as infiltration and increased proliferative activity. Both the initially resected and recurrent tumor revealed MYBL1-MMP16 fusion, which is much more commonly found in pediatric low-grade gliomas and, to our knowledge has not been described in the context of an adult glioma. Conclusion: The significance of MYBL1-MMP16 fusion in adult gliomas in relation to survival and likelihood of recurrence is, therefore, unknown and requires more extensive research.

Pediatric-type diffuse low-grade gliomas.

The World Health Organization's 5th edition classification of Central Nervous System (CNS) tumors differentiates diffuse gliomas into adult and pediatric variants. Pediatric-type diffuse low-grade gliomas (pDLGGs) are distinct from adult gliomas in their molecular characteristics, biological behavior, clinical progression, and prognosis. Various molecular alterations identified in pDLGGs are crucial for treatment. There are four distinct entities of pDLGGs. All four of these tumor subtypes exhibit diffuse growth and share overlapping histopathological and imaging characteristics. Molecular analysis is essential for differentiating these lesions.

Comprehensive analysis of MYB/MYBL1-altered pediatric-type diffuse low-grade glioma.

BACKGROUND: Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies. METHODS: We retrospectively reviewed details of pLGG with MYB or MYBL1 alterations from patients treated or referred for pathologic review at St. Jude Children's Research Hospital. Tumor specimens were centrally reviewed, and clinical data were collated. RESULTS: Thirty-three patients (18 male; median age, 5 years) were identified. Two tumors had MYBL1 alterations; 31 had MYB alterations, MYB::QKI fusion being the most common (n = 10, 30%). Most tumors were in the cerebral hemispheres (n = 22, 67%). Two patients (6%) had metastasis at diagnosis. The median follow-up was 6.1 years. The 5-year event-free survival (EFS) rate was 81.3% ±â€…8.3%; the 5-year overall survival (OS) rate was 96.4% ±â€…4.1%. Patients receiving a near-total or gross-total resection had a 5-year EFS of 100%; those receiving a biopsy or subtotal resection had a 5-year EFS rate of 56.6% ±â€…15.2% (P < .01). No difference in EFS was observed based on location, histology, or molecular alterations. However, the tumors that progressed or metastasized may have distinct methylation profiles with evidence of activation of the MAPK and PI3K/AKT/mTOR pathways. CONCLUSIONS: pLGG with MYB/MYBL1 alterations have good outcomes. Our findings suggest that surgical resectability is a crucial determinant of EFS. Further characterization is required to identify optimal treatment strategies for progressive tumors.

Characterization of MYBL1 Gene in Triple-Negative Breast Cancers and the Genes' Relationship to Alterations Identified at the Chromosome 8q Loci.

The MYBL1 gene is a strong transcriptional activator involved in events associated with cancer progression. Previous data show MYBL1 overexpressed in triple-negative breast cancer (TNBC). There are two parts to this study related to further characterizing the MYBL1 gene. We start by characterizing MYBL1 reference sequence variants and isoforms. The results of this study will help in future experiments in the event there is a need to characterize functional variants and isoforms of the gene. In part two, we identify and validate expression and gene-related alterations of MYBL1, VCIP1, MYC and BOP1 genes in TNBC cell lines and patient samples selected from the Breast Invasive Carcinoma TCGA 2015 dataset available at cBioPortal.org. The four genes are located at chromosomal regions 8q13.1 to 8q.24.3 loci, regions previously identified as demonstrating a high percentage of alterations in breast cancer. We identify alterations, including changes in expression, deletions, amplifications and fusions in MYBL1, VCPIP1, BOP1 and MYC genes in many of the same patients, suggesting the panel of genes is involved in coordinated activity in patients. We propose that MYBL1, VCPIP1, MYC and BOP1 collectively be considered as genes associated with the chromosome 8q loci that potentially play a role in TNBC pathogenesis.

Adenoid cystic carcinoma of the Bartholin's gland is underpinned by MYB- and MYBL1- rearrangements.

OBJECTIVE: Adenoid cystic carcinoma (AdCC) of the Bartholin's gland (AdCC-BG) is a very rare gynecologic vulvar malignancy. AdCC-BGs are slow-growing but locally aggressive and are associated with high recurrence rates. Here we sought to characterize the molecular underpinning of AdCC-BGs. METHODS: AdCC-BGs (n = 6) were subjected to a combination of RNA-sequencing, targeted DNA-sequencing, reverse-transcription PCR, fluorescence in situ hybridization (FISH) and MYB immunohistochemistry (IHC). Clinicopathologic variables, somatic mutations, copy number alterations and chimeric transcripts were assessed. RESULTS: All six AdCC-BGs were biphasic, composed of ductal and myoepithelial cells. Akin to salivary gland and breast AdCCs, three AdCC-BGs had the MYB::NFIB fusion gene with varying breakpoints, all of which were associated with MYB overexpression by IHC. Two AdCC-BGs were underpinned by MYBL1 fusion genes with different gene partners, including MYBL1::RAD51B and MYBL1::EWSR1 gene fusions, and showed MYB protein expression. Although the final AdCC-BG studied had MYB protein overexpression, no gene fusion was identified. AdCC-BGs harbored few additional somatic genetic alterations, and only few mutations in cancer-related genes were identified, including GNAQ, GNAS, KDM6A, AKT1 and BCL2, none of which were recurrent. Two AdCC-BGs, both with a MYB::NFIB fusion gene, developed metastatic disease. CONCLUSIONS: AdCC-BGs constitute a convergent phenotype, whereby activation of MYB or MYBL1 can be driven by the MYB::NFIB fusion gene or MYBL1 rearrangements. Our observations further support the notion that AdCCs, irrespective of organ site, constitute a genotypic-phenotypic correlation. Assessment of MYB or MYBL1 rearrangements may be used as an ancillary marker for the diagnosis of AdCC-BGs.

Molecular characterisation of tumours of the lacrimal apparatus.

AIMS: Malignant tumours of the lacrimal apparatus are rare and frequently show a poor prognosis, with no clear therapeutic standards. Characterisation of the genetic landscape of these rare tumours is sparse, and therefore therapeutics generally follow those of their common salivary gland counterparts. To further clarify the pathophysiology and discover potential therapeutic targets, we investigated the genetic landscape of eight tumours of the lacrimal apparatus. METHODS AND RESULTS: DNA and RNA sequencing were performed to identify genetic mutations and gene fusions. Immunohistochemistry, fluorescence in-situ hybridisation and reverse transcription-polymerase chain reaction followed by Sanger sequencing were performed to confirm the identified molecular alterations. Genetic alterations were detected in six tumours. Among five adenoid cystic carcinomas (ACC), four had confirmed alterations of MYB or MYBL1 genes, including a MYB::NFIB fusion, a MYBL1::NFIB fusion, a MYB amplification and a novel NFIB::THSD7B fusion. Mutations in genes encoding epigenetic modifiers, as well as NOTCH1, FGFR2 and ATM mutations, were also identified in ACCs. A carcinoma ex pleomorphic adenoma showed TP53 and CIC mutations and an amplification of ERBB2. A transitional cell carcinoma was associated with HPV16 infection. No genetic alteration was found for one adenocarcinoma, not otherwise specified. CONCLUSIONS: Our study highlights the variety of molecular alterations associated with lacrimal system tumours and emphasises the importance of molecular testing in these tumours, which can reveal potentially targetable mutations. Our results also reinforce the hypothesis of a common physiopathology of all ACCs, regardless of their primary location.

The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

miR-145-3p Inhibits MuSCs Proliferation and Mitochondria Mass via Targeting MYBL1 in Jianzhou Big-Eared Goats.

Muscle growth and injury-induced regeneration are controlled by skeletal muscle satellite cells (MuSCs) through myogenesis in postnatal animals. Meanwhile, myogenesis is accompanied by mitochondrial function and enzyme activity. Nevertheless, the underlying molecular mechanisms involving non-coding RNAs including circular RNAs (circRNAs) and microRNAs (miRNAs) remain largely unsolved. Here, we explored the myogenic roles of miR-145-3p and MYBL1 on muscle development and mitochondrial mass. We noticed that overexpression of miR-145-3p inhibited MuSCs proliferation and reduced the number of viable cells. Meanwhile, deficiency of miR-145-3p caused by LNAantimiR-145-3p or an inhibitor retarded the differentiation of MuSCs. miR-145-3p altered the mitochondrial mass in MuSCs. Moreover, miR-145-3p targeted and negatively regulated the expression of CDR1as and MYBL1. The knockdown of the MYBL1 using ASO-2'MOE modification simulated the inhibitory function of miR-145-3p on cell proliferation. Additionally, MYBL1 mediated the regulation of miR-145-3p on Vexin, VCPIP1, COX1, COX2, and Pax7. These imply that CDR1as/miR-145-3p/MYBL1/COX1, COX2, VCPIP1/Vexin expression at least partly results in a reduction in mitochondrial mass and MuSCs proliferation. These novel findings confirm the importance of mitochondrial mass during myogenesis and the boosting of muscle/meat development in mammals.

Evaluation of MYBL1 as the master regulator for pachytene spermatocyte genes dysregulated in interspecific hybrid dzo.

Misregulation of spermatogenesis transcription factors (TF) in hybrids can lead to misexpression, which is a mechanism for hybrid male sterility (HMS). We used dzo (male offspring of Bos taurus ♂ × Bos grunniens ♀) in bovines to investigate the relationship of the key TF with HMS via RNA sequencing and assay for transposase-accessible chromatin with high-throughput sequencing analyses. RNA sequencing showed that the widespread misexpression in dzo was associated with spermatogenesis-related genes and somatic or progenitor genes. The transition from leptotene or zygotene spermatocytes to pachytene spermatocytes may be the key stage for meiosis arrest in dzo. The analysis of TF-binding motif enrichment revealed that the male meiosis-specific master TF MYB proto-oncogene like 1 (MYBL1, known as A-MYB) motif was enriched on the promoters of downregulated pachytene spermatocyte genes in dzo. Assay for transposase-accessible chromatin with high-throughput sequencing revealed that TF-binding sites for MYBL1, nuclear transcription factor Y, and regulatory factor X were enriched in the low-chromatin accessibility region of dzo. The target genes of the MYBL1-binding motif were associated with meiosis-specific genes and significantly downregulated in dzo testis. The transcription factor MYBL1 may be the candidate master regulator for pachytene spermatocyte genes dysregulated in interspecific HMS dzo. This study reported that a few upstream TF regulation changes might exert a cascading effect downstream in a regulatory network as a mechanism for HMS.

MYB/MYBL1::QKI fusion-positive diffuse glioma.

The MYB/MYBL1::QKI fusion induces the protooncogene, MYB, and deletes the tumor suppressor gene, QKI. MYB/MYBL1::QKI rearrangement was previously reported only in angiocentric glioma (AG) and diffuse low-grade glioma. This report compares 2 tumors containing the MYB/MYBL1::QKI fusion: a diffuse pediatric-type high-grade glioma (DPedHGG) in an 11-year-old boy and an AG in a 46-year-old woman. We used immunohistochemistry, next-generation sequencing, and methylation profiling to characterize each tumor and compare our findings to the literature on AG and tumors with the MYB/MYBL1::QKI rearrangement. Both tumors were astrocytic with angiocentric patterns. The MYB::QKI fusion-positive DPedHGG, which recurred once, was accompanied by TP53 mutation and amplification of CDK6 and KRAS, suggesting malignant transformation secondary to additional genetic aberrations. The second case was the adult AG with MYBL1::QKI fusion, which mimicked ependymoma based on histopathology and its dot- and ring-like epithelial membrane antigen positivity. Combined with a literature review, our results suggest that MYB/MYBL1 alterations are not limited to low-grade gliomas, including AG. AG is most common in the cerebra of children and adolescents but exceptional cases occur in adults and the acquisition of additional genetic mutations may contribute to high-grade glioma. These cases further demonstrate that molecular characteristics, morphologic features, and clinical context are essential for diagnosis.

Adenoid cystic carcinoma in children and young adults: A clinicopathological study of 12 cases.

OBJECTIVE: To investigate the clinicopathological characteristics, immunoprofile, and molecular alterations of adenoid cystic carcinoma (ACC) in children and young adults. MATERIALS AND METHODS: Twelve cases of ACC were included. MYB, MYBL1, Ki-67, type IV Collagen, Laminin, and LAMB1 expression were detected by immunohistochemistry. MYB and MYBL1 rearrangements were detected by fluorescence in situ hybridization. RESULTS: Among 12 patients, four were female and eight were male. Seven cases (58.3%) located in major salivary glands and eight cases (66.7%) were classified as Grade I. Ten tumors (83.3%) had collagenous and hyalinized stroma. MYB was positive in 83.3% cases, and the average Ki-67 labeling index (LI) was 8.3%. LAMB1, type IV Collagen, and Laminin were positive in 91.7%, 66.7%, and 58.3% cases, respectively. Besides, three out of eight tumors had MYB rearrangement. Cases without MYB rearrangement were negative for MYBL1 expression and MYBL1 rearrangement. The average follow-up time was 91.8 months. Four patients had recurrent diseases. CONCLUSIONS: ACC in children and young adults was seen more frequently in males and major salivary glands. Most cases had ECM and hyaline stroma. Grade III tumors, higher Ki-67 LI, negative expression of type IV Collagen, and Laminin showed a tendency of higher recurrence rate.

Pediatric-type diffuse low-grade glioma with MYB/MYBL1 alteration: report of 2 cases.

2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) has shown how molecular features can impact the classification of brain tumors. The continued combination of molecular features with histopathology has led to distinguish tumors with similar histopathologic features but distinct clinical prognosis. The 2021 revised 5. edition of the WHO classification further includes molecular features for CNS tumor categorization including MYB/MYBL1 altered diffuse astrocytoma which is a newly recognized type of low-grade pediatric-type brain tumor. We discuss imaging features of two pediatric-type low-grade gliomas with MYB/MYBL1-mutation that encountered at our institution.

LncRNA ENSMUST00000171502 Induced by HIF-1α Ameliorates Ischemic Acute Kidney Injury via Targeting the miR-130b-3p/Mybl-1 Axis.

Background: Numerous studies have suggested that long non-coding RNA (lncRNA) affects the progression of ischemic acute kidney injury (IAKI). However, little information is currently available concerning the mechanisms of lncRNA171502 involved in IAKI. Methods: We applied an RT-qPCR assay for the expression of lncRNA171502 and miRNA-130b-3p, immunoblotting for the detection of Mybl-1-myeloblastosis oncogene-like 1 (Mybl-1) and cleaved caspase-3 (CC3) expression, and flow cytometry (FCM) for the evaluation of apoptosis. Result: Initially, lncRNA171502 was induced by HIF-1α in the mouse proximal tubular (BUMPT) cell line and C57BL/6J mice during ischemic injury. Secondly, ischemic injury-induced BUMPT cell apoptosis was markedly relieved following the overexpression of lncRNA171502. However, this effect was enhanced by the knockdown of lncRNA171502. Mechanistically, lncRNA171502 could sponge miRNA-130b-3p and would subsequently upregulate the expression of Mybl-1 to drive the apoptotic process. Lastly, the overexpression of lncRNA171502 alleviated the development of IAKI by targeting miRNA-130b-3p/Mybl-1 pathways. Conclusions: In summary, the HIF-1α/lncRNA171502/miRNA-130b-3p/Mybl-1 axis prevented the progression of IAKI and might serve as a potential therapeutic target.

Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome.

The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise in children (defined as "paediatric") based on clinical and molecular characteristics."). However, paediatric-type gliomas may occasionally be present in younger adults and occasionally adult-type gliomas may occur in children. Diffuse low-grade paediatric glioma includes diffuse astrocytoma altered by MYB or MYBL1, low-grade polymorphic juvenile neuroepithelial tumour, angiocentric glioma, and diffuse low-grade glioma with an altered MAPK pathway. Here, we examine these newly recognised entities according to WHO diagnostic criteria and propose an integrated diagnostic approach that can be used to separate these clinically and biologically distinct tumor groups.

Rearrangements, Expression, and Clinical Significance of MYB and MYBL1 in Adenoid Cystic Carcinoma: A Multi-Institutional Study.

Adenoid cystic carcinoma (ACC) is an aggressive head and neck malignancy characterized by a t (6;9) translocation resulting in an MYB-NFIB gene fusion or, more rarely, an MYBL1 fusion. The true frequency and clinical significance of these alterations are still unclear. Here, we have used tissue microarrays and analyzed 391 ACCs and 647 non-ACC salivary neoplasms to study the prevalence, expression, and clinical significance of MYB/MYBL1 alterations by FISH and immunohistochemistry. Alterations of MYB or MYBL1 were found in 78% of the cases, of which 62% had MYB alterations and 16% had MYBL1 rearrangements. Overexpression of MYB/MYBL1 oncoproteins was detected in 93% of the cases. MYB split signal, seen in 39% of the cases, was specific for ACC and not encountered in non-ACC salivary tumors. Loss of the 3'-part of MYB was enriched in grade 3 tumors and was a significant independent prognostic biomarker for overall survival in multivariate analyses. We hypothesize that loss of the 3'-part of MYB results from an unbalanced t(6;9) leading to an MYB-NFIB fusion with concomitant loss of the segment distal to the MYB breakpoint in 6q23.3. Our study provides new knowledge about the prevalence and clinical significance of MYB/MYBL1 alterations and indicates the presence of genes with tumor suppressive functions in 6q23.3-qter that contribute to poor prognosis and short overall survival in ACC.

Genetic Alteration Analysis of IDH1, IDH2, CDKN2A, MYB and MYBL1 in Pediatric Low-Grade Gliomas.

Objective: To investigate pediatric low-grade gliomas for alterations in IDH1, IDH2, CDKN2A, MYB, and MYBL1. Materials and Methods: DNA and RNA were extracted from 62 pediatric gliomas. Molecular methods included PCR, RT-PCR, and RNA sequencing; Sanger sequencing was used for validation. Results: Analysis for hotspot genetic alterations in IDH1 R132 and IDH2 R172 (45 and 33 samples) was negative in all cases. CDKN2A deletions were detected in exons 1 and 2 in 1 (pleomorphic xanthoastrocytoma) sample of 9 samples analyzed. Of 10 samples analyzed for MYB translocation, 4 each were positive for translocations with exon 2 and exon 3 of PCDHGA1. Six samples showed MYBL rearrangement. The lack of IDH1/2 genetic alterations is in accordance with the literature in pediatric tumors. Alterations in MYB, MYBL were recently reported to characterize diffuse grade II, but not grade I, gliomas. Conclusion: We optimized methods for analyzing gene variations and correlated the findings to pathological grade. The high incidence of MYB and MYBL need further evaluation. We also compared DNA, RNA, and RNA sequencing results for fusion, translocation, and genetic alterations. More accurate identification of the underlying biology of pediatric gliomas has implications for the development of targeted treatment.

Recent Advances on Immunohistochemistry and Molecular Biology for the Diagnosis of Adnexal Sweat Gland Tumors.

Cutaneous sweat gland tumors are a subset of adnexal neoplasms that derive or differentiate into the sweat apparatus. Their great diversity, rarity, and complex terminology make their pathological diagnosis challenging. Recent findings have revealed a wide spectrum of oncogenic drivers, several of which are of diagnostic interest for pathologists. Most of these molecular alterations are represented by gene fusions, which are shared with other homologous neoplasms occurring in organs containing exocrine glands, such as salivary and breast glands, which show similarities to the sweat apparatus. This review aims to provide a synthesis of the most recent immunohistochemical and molecular markers used for the diagnosis of sweat gland tumors and to highlight their relationship with similar tumors in other organs. It will cover adenoid cystic carcinoma (NFIB, MYB, and MYBL1 fusion), cutaneous mixed tumor (PLAG1 fusion), cylindroma and spiradenoma and their carcinomas thereof (NF-κB activation through CYLD inactivation or ALKP1 hotspot mutation), hidradenoma and hidradenocarcinoma (MAML2 fusion), myoepithelioma (EWSR1 and FUS fusion), poroma and porocarcinoma (YAP1, MAML2, and NUTM1 fusion), secretory carcinoma (ETV6, NTRK3 fusion), tubular adenoma and syringo-cystadenoma papilliferum (HRAS and BRAF activating mutations). Sweat gland tumors for which there are no known molecular abnormalities will also be briefly discussed, as well as potential future developments.

Integration analysis identifies MYBL1 as a novel immunotherapy biomarker affecting the immune microenvironment in clear cell renal cell carcinoma: Evidence based on machine learning and experiments.

Background: Previous studies have identified MYBL1 as a cancer-promoting molecule in numerous types of cancer. Nevertheless, the role of MYBL in renal cancer remains unclear. Methods: Genomic and clinical data of clear cell renal cell carcinoma (ccRCC) was get from the Cancer Genome Atlas (TCGA) database. CCK8, colony formation, and 5-ethynyl-2'-deoxyuridine assay were utilized to evaluate the performance of cell proliferation. Cell apoptosis was detected using the flow cytometric analysis. The protein level of MYBL1 in different tissues was evaluated using immunohistochemistry. A machine learning algorithm was utilized to identify the prognosis signature based on MYBL1-derived molecules. Results: Here, we comprehensively investigated the role of MYBL1 in ccRCC. Here, we noticed a higher level of MYBL1 in ccRCC patients in both RNA and protein levels. Further analysis showed that MYBL1 was correlated with progressive clinical characteristics and worse prognosis performance. Biological enrichment analysis showed that MYBL1 can activate multiple oncogenic pathways in ccRCC. Moreover, we found that MYBL1 can remodel the immune microenvironment of ccRCC and affect the immunotherapy response. In vitro and in vivo assays indicated that MYBL1 was upregulated in ccRCC cells and can promote cellular malignant behaviors of ccRCC. Ultimately, an machine learning algorithm - LASSO logistics regression was utilized to identify a prognosis signature based on the MYBL1-derived molecules, which showed satisfactory prediction ability on patient prognosis in both training and validation cohorts. Conclusions: Our result indicated that MYBL1 is a novel biomarker of ccRCC, which can remodel the tumor microenvironment, affect immunotherapy response and guide precision medicine in ccRCC.

[Low grade glioma with MYBL1 alteration: Case report of an uncommon pediatric neoplasm]. / Gliome de bas grade avec altération de MYBL1 : observation d'une nouvelle entité tumorale pédiatrique.

Diffuse gliomas with MYB or MYBL1 alterations are rare tumours mostly affecting children or young adults with long-term epilepsy. This category of glioma includes two morphological subtypes. The angiocentric subtype is characterized by an angiocentric pattern of growth and a frequent MYB:QKI fusion. The isomorphic subtype corresponds to a highly differentiated astrocytic glioma with low cellularity, low proliferation and no specific microscopic features. The diagnosis is based on the imaging, demonstrating a supratentorial tumor, associated with the confirmation of a MYB or MYBL1 rearrangement. Here, we report the case of a 7-year-old child who presented a right frontal brain lesion corresponding to an isomorphic diffuse glioma with MYBL1 alteration.

MYB Proto-oncogene-like 1-TWIST1 Axis Promotes Growth and Metastasis of Hepatocellular Carcinoma Cells.

MYB proto-oncogene-like 1 (MYBL1) has been reported to be a strong activator of transcription and plays an important role in the development of cancer. However, the precise biological function and molecular mechanism of MYBL1 in hepatocellular carcinoma (HCC) cells remain unclear. In the present study, we found that the expression of MYBL1 was markedly overexpressed in HCC cell lines and HCC samples, respectively. Moreover, MYBL1 expression positively correlated with tumor progression and inversely correlated with patient survival in 368 human HCC tissue samples. Overexpression of MYBL1 induced, whereas knockdown of MYBL1 reduced, HCC proliferation and metastasis both in vitro and in vivo. Furthermore, we demonstrated that HCC patients with high MYBL1 expression had significantly shorter overall and poorer disease-free survival than those with low MYBL1 expression. MYBL1 transcriptionally upregulated TWIST1 expression by directly targeting the TWIST1 promoter. More importantly, the in vitro analysis was consistent with the significant correlation between MYBL1 and TWIST1 expression observed in a large cohort of human HCC specimens. Taken together, our results demonstrate that MYBL1 plays an important role in HCC growth and metastasis and reveal a plausible mechanism for upregulation of TWIST1 in HCC.