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Arginine methylation is an important posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs). However, the role of PRMTs in colorectal cancer (CRC) progression is not well understood. Here we report that non-POU domain-containing octamer-binding protein (NONO) is overexpressed in CRC tissue and is a potential marker for poor prognosis in CRC patients. NONO silencing resulted in decreased proliferation, migration, and invasion of CRC cells, whereas overexpression had the opposite effect. In a xenograft model, tumors derived from NONO-deficient CRC cells were smaller than those derived from wild-type (WT) cells, and PRMT1 inhibition blocked CRC xenograft progression. A mass spectrometry analysis indicated that NONO is a substrate of PRMT1. R251 of NONO was asymmetrically dimethylated by PRMT1 in vitro and in vivo. Compared to NONO WT cells, NONO R251K mutant-expressing CRC cells showed reduced proliferation, migration, and invasion, and PRMT1 knockdown or pharmacological inhibition abrogated the malignant phenotype associated with NONO asymmetric dimethylation in both KRAS WT and mutant CRC cells. Compared to adjacent normal tissue, PRMT1 was highly expressed in the CRC zone in clinical specimens, which was correlated with poor overall survival in patients with locally advanced CRC. These results demonstrate that PRMT1-mediated methylation of NONO at R251 promotes CRC growth and metastasis, and suggest that PRMT1 inhibition may be an effective therapeutic strategy for CRC treatment regardless of KRAS mutation status.

Here we reported a pedigree that gave birth to two characteristic clinical signs of Kabuki syndrome daughters. They had an intellectual disability with special facial features. Their eyebrows were relatively wide and the rear 1/3 of the eyebrows were light and sparse. Their eyes were long, narrow, valgus and strabismus. Their noses were broad at the root and flat at the tip. They also had skeletal dysplasia, mainly manifested in the short second knuckle of the little fingers of both hands. Genetic studies showed a novel de novo KMT2D variant (c.16343G C; p.R5448P) as a cause of Kabuki syndrome. It was very unlikely that the same de novo mutation occurred in two members of a family. Gonadal mosaicism in one of the parents was suspected. Haplotype construction and clone sequencing were used for mutation source analysis. Finally, we inferred that the haplotype from the mother (Gdel-G-C-T-A) contained the pathogenic mutation. A gonadal mosaicism novel KMT2D mutation was identified in their mother.

Epstein-Barr virus nuclear antigen 2 (EBNA2) is a transactivator of viral and cellular gene expression, which plays a critical role in the Epstein-Barr virus-associated diseases. It was reported that EBNA2 regulates gene expression by reorganizing chromatin and manipulating epigenetics. Recent studies showed that liquid-liquid phase separation plays an essential role in epigenetic and transcriptional regulation. Here we show that EBNA2 reorganized chromatin topology to form accessible chromatin domains (ACDs) of the host genome by phase separation. The N-terminal region of EBNA2, which is necessary for phase separation, is sufficient to induce ACDs. The C-terminal domain of EBNA2 promotes the acetylation of accessible chromatin regions by recruiting histone acetylase p300 to ACDs. According to these observations, we proposed a model of EBNA2 reorganizing chromatin topology for its acetylation through phase separation to explain the mechanism of EBNA2 hijacking the host genome by controlling its epigenetics., Yang et al find that phase separation of the Epstein-Barr virus nuclear antigen 2 (EBNA2) is involved in the formation of accessible chromatin domains of the host genome. They also find that EBNA2 recruits histone acetyltransferase to promote histone acetylation on accessible chromatin regions and regulate gene expression and that these two functions are performed by the N- and Cterminus respectively.

The rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-mediated DSB repair. The intrinsically disordered region is essential for MRNIP condensate formation. Mechanically, the MRN complex is compartmentalized and concentrated into MRNIP condensates in the nucleus. After DSB formation, MRNIP condensates move to the damaged DNA rapidly to accelerate the binding of DSB by the concentrated MRN complex, therefore inducing the autophosphorylation of ATM and subsequent activation of DNA damage response signaling. Meanwhile, MRNIP condensates-enhanced MRN complex loading further promotes DSB end resection. In addition, data from xenograft models and clinical samples confirm a correlation between MRNIP and radioresistance. Together, these results reveal an important role of MRNIP phase separation in DSB response and the MRN complex-mediated DSB end resection.

Retinitis pigmentosa 77 is caused by mutations of REEP6 (MIM: 609346), which encodes a protein for the development of photoreceptors. Our study was to identify disease-causing variants in three Chinese families using targeted next-generation sequencing (NGS). Multiple lines of computational predictions combined with in vitro cellular experiments were applied to evaluate the pathogenicity of the newly found variants. Three novel variants in REEP6, including one missense variant, c.268G&gt, C, one frameshift variant, c.468delC, and one splicing variant, c.598+1G&gt, C, were found, while c.268G&gt, C was detected in all probands. The three variants were classified as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG). REEP6 variant proteins c.268G&gt, C and c.468delC in cultured cells destabilized the REEP6 protein and induced intracellular inclusions. Our data suggested that REEP6 c.268G&gt, C may be a recurrent causative variant in Chinese autosomal recessive retinitis pigmentosa patients.

To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4).Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing.DNA sequencing suggested that the proband has carried a heterozygous c.1196CG variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic.The c.1196CG variant of the SPAST gene probably underlay the HSP4 in this pedigree.

Cohen syndrome (CS) is an autosomal recessive congenital disorder characterized by mutation in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. In the current study, a Chinese family has two young sibling cases having a developmental delay, physical obesity, high myopia, and a special face, which suspected to be CS. The purpose of the study was to identify variants and further analyze their pathogenicity for CS. Next-generation sequencing (NGS) revealed a compound heterozygous mutation in VPS13B gene in the proband, which comprises a frameshift mutation in NM_017890.4: c.10076_10077delCA (p.T3359fs*29) and a putative splice site mutation in c.6940 + 1G T. Both Minigene assay in vitro and splicing assay in vivo confirmed that the splicing mutation in c.6940 + 1G T generates a frameshift transcript with whole exon 38 skipping. Eventually, quantitative real-time PCR demonstrated that either of the two mutations can lead to degradation of the VPS13B gene at the transcriptional level. Functional studies of variants identified in CS patients are essential for their subsequent genetic counseling and prenatal diagnoses and could also be the start point for new therapeutic approaches, currently based only on symptomatic treatment.

Long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of various cancers, including laryngeal squamous cell carcinoma (LSCC). Recently, lncRNA Sox2 overlapping transcript (SOX2-OT) has been identified as an oncogene in various cancers. However, the functional role and the regulatory mechanism of SOX2-OT in LSCC remains unclear. In this study, we found that SOX2-OT expression was increased and negatively correlated with PTEN expression in LSCC tissues. Furthermore, SOX2-OT overexpression promoted LSCC cell proliferation, migration, invasion, and suppressed cell apoptosis in vitro, as well as facilitated the in vivo tumorigenicity. By contrast, SOX2-OT silencing exerted the opposite effect. Mechanically, SOX2-OT interacted with EZH2 and recruited EZH2 to induce H3K27me3 and epigenetically inhibited PTEN expression in LSCC cells. Additionally, EZH2 silencing and PTEN overexpression significantly abrogated the SOX2-OT overexpression-mediated promotion of LSCC cell malignant behavior. Collectively, our findings demonstrate that SOX2-OT inhibits PTEN expression to facilitate LSCC development through EZH2-mediated H3K27me3. © 2019 IUBMB Life, 71(9):1230-1239, 2019.

Identification of genomic alterations from formalin-fixed paraffin-embedded (FFPE) samples using next-generation sequencing (NGS) is very important for cancer-targeted therapy today. To achieve a higher efficiency and shorter turn-around time for NGS library preparation, here, we compared NGS library preparation processes and outcomes with three commercial library construction methods and two hybridization capture methods thus, developed an improved NGS library construction approach. This improved approach took advantage of both methods and resulted in a higher output from the same input DNA, including higher library construction success rate, higher probe capture rate, and shorter turn-around time. Using this approach, targeted region libraries could be constructed within only 1 day for FFPE samples; therefore, this approach has potential applications of NGS in routine clinical tests. Anat Rec, 302:941-946, 2019. © 2018 Wiley Periodicals, Inc.

Congenital hand malformations is rare and characterized by hand deformities. It is highly heterogeneous, both clinically and genetically, which complicates the identification of causative genes and mutations. Recently, targeted next-generation (NGS) sequencing has been successfully used for the detection of heterogeneous diseases, and the use of NGS also has contributed significantly in evaluating the etiology of heterogeneous disease. Here, we employed targeted NGS to screen 248 genes involved in genetic skeletal disorders, including congenital hand malformations. Three pathogenic mutations located in the GJA1, ROR2 and TBX5 genes were detected in three large Chinese families with congenital hand malformations. Two novel mutations were reported, and a known causative mutation was verified in this Chinese population. This is also the first report that the same panel of targeted NGS was employed to perform molecular diagnosis of different subtypes of congenital hand malformations. Our study supported the application of a targeted NGS panel as an effective tool to detect the genetic cause for heterogeneous diseases in clinical diagnosis.

Donohue syndrome (DS), a rare autosomal recessive disease which represents severe insulin resistance, pre- and postnatal growth retardation, hypertrichosis, and dysmorphic features, is caused by mutations in the insulin receptor (INSR) gene. Here, we have reported the clinical, molecular, and biochemical characterizations of a patient with DS. In this article, we have also reported a case with 2 novel INSR mutations and the DS phenotype. Using next-generation sequencing (NGS), we screened 27 known genes involved in inherited maturity-onset diabetes of the young (MODY) and identified compound heterozygous mutations in the INSR gene in the patient with DS, c.62T>G (p.L21R) and c.2563G>T (p.V855F). The positive correlation of these mutations with DS was further validated by Sanger DNA sequencing of his lineal consanguinity, indicating that these pathogenic mutations were inherited maternally and paternally, respectively. Therefore, our finding expanded the number of reported cases of this rare disease and the mutation spectrum of INSR mutation, suggesting that NGS is an accurate, rapid, and cost-effective method for the genetic diagnosis of this rare disease.

To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF).Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing.The fetus was found to carry compound heterozygous variants c.1440+1GA and c.925GT of the NPHS1 gene, which were respectively inherited from its mother and father.Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.

To explore the genetic basis for a family with non-syndromic autosomal recessive deafness.The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents.The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c.462CA (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father.The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.

To explore the clinical and genetic features of a patient suspected with Juvenile Parkinson's syndrome (JP).Clinical features of the patient were analyzed. Genomic DNA of the patient and his parents was extracted from peripheral blood samples and sequenced by exome capture sequencing. The nature and impact of detected mutations were predicted and validated.The patient displayed typical features including resting tremor, bradykinesia, rigidity, but with excellent response to low dose levodopa. DNA sequencing showed that she has carried compound heterozygous mutations of the Parkin gene, namely c.1381dupC and c.619-1GC, which were respectively inherited from his mother and father. Neither mutation was reported previously. Bioinformatic analysis predicted that both mutations are pathogenic.The patient has JP caused by mutations of the Parkin gene. Exome capture sequencing is an accurate and efficient method for genetic diagnosis of such disease.

Introduction Adams-Oliver syndrome (AOS) is a rare developmental disorder characterized by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects. DOCK6 (Dedicator of cytokinesis 6) is one of the six identified AOS genes. Methods We performed targeted next-generation sequencing (NGS) of a child with an AOS phenotype. Sanger DNA sequencing further validated her lineal consanguinity. To explore the pathological features of the mutation, a minigene assay was used to investigate the effects of the mutation on splicing. Results Two compound heterozygous DOCK6 mutations (c.4106+2T>C and c.3063 C>G (p.Y1021*)) were identified in this family, and both mutations have not been reported previously. Sanger DNA sequencing indicated that the mutations were inherited maternally and paternally, respectively. The results of the minigene assay showed that the c.4106+2T>C mutation resulted in aberrant splicing and caused a four-nucleotide insertion in the transcript and a premature stop codon. Conclusions Our findings expanded the number of reported cases of this rare disease and the mutation spectrum of DOCK6 mutations, which can serve as the basis for prenatal diagnosis and genetic counseling.

Identification of genes with variants causing non-syndromic hearing loss (NSHL) is challenging due to genetic heterogeneity. The difficulty is compounded by technical limitations that in the past prevented comprehensive gene identification. Recent advances in technology, using targeted capture and next-generation sequencing (NGS), is changing the face of gene identification and making it possible to rapidly and cost-effectively sequence the whole human exome. Here, we characterize a five-generation Chinese family with progressive, postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining population-specific mutation arrays, targeted deafness genes panel, whole exome sequencing (WES), we identified PDE1C (Phosphodiesterase 1C) c.958G>T (p.A320S) as the disease-associated variant. Structural modeling insights into p.A320S strongly suggest that the sequence alteration will likely affect the substrate-binding pocket of PDE1C. By whole-mount immunofluorescence on postnatal day 3 mouse cochlea, we show its expression in outer (OHC) and inner (IHC) hair cells cytosol co-localizing with Lamp-1 in lysosomes. Furthermore, we provide evidence that the variant alters the PDE1C hydrolytic activity for both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Collectively, our findings indicate that the c.958G>T variant in PDE1C may disrupt the cross talk between cGMP-signaling and cAMP pathways in Ca2+ homeostasis.

To detect potential mutation in a Chinese pedigree affected with familial exudative vitreoretinopathy (FEVR).Clinical data of the pedigree was collected. Coding regions of candidate genes were amplified by PCR and subjected to next generation sequencing (NGS). Suspected mutations were verified by Sanger sequencing and segregation analysis.Two novel heterozygous mutations (c.1695dupC and c.552-563del) were respectively detected in the LRP5 and ZNF408 genes in the proband. Both mutations were inherited from the affected mother. By Sanger sequencing, the c.552-563del mutation was also detected among unaffected members, while the c.1695dupC mutation was only detected in affected members from the pedigree and was not recorded by the HGMD, NCBI, or 1000 genome database. Upon prenatal diagnosis, the fetus was found to carry the same mutations.Combined NGS and Sanger sequencing not only can reduce the time required for diagnosis but also enable accurate prenatal diagnosis for FEVR.

OBJECTIVE To detect potential mutations of the EXT1 and EXT2 genes in a pedigree affected with hereditary multiple exostosis (HME). METHODS For a four-generation family with 7 affected individuals from 17 family members,genomic DNA was extracted from peripheral venous blood samples. All exons of the EXT1 and EXT2 genes were screened for potential mutation by PCR and Sanger sequencing. RESULTS A novel heterozygous frameshift mutation c.1202delT (p.I401Tfs*2)was found in exon 4 of the EXT1 gene in the proband and the other 6 affected individuals. The same mutation was not detected among the healthy members from the family. The mutation has given rise a truncated EXT1 protein with loss of 345 amino acids. CONCLUSION A novel frameshift mutation of the EXT1 gene has been identified in a pedigree affected with HME, which has enriched the mutational spectrum of the EXT1 gene and may facilitate genetic counseling and prenatal diagnosis for the family.

We determined whether a child with 17α-hydroxylase/17, 20-lyase deficiency possessed the sex-determining region (SRY) gene, and examined the mutations present in the CYP17A1 gene that led to 17α-hydroxylase/17, 20-lyase deficiency. In the child, karyotype analysis was performed and polymerase chain reaction analysis and electrophoretic techniques were used to identify the SRY gene. A total of 50 normal individuals were included as a control group. Polymerase chain reaction and DNA sequencing were used to identify CYP17A1 gene mutations in all samples. The karyotype of the child was 46, XY, which was inconsistent with her social sex, SRY was positive, and a compound heterozygous mutation p. Thr101Ilefs*2 in exon 2 and p. Thr306Ale in exon 5 were identified in the CYP17A1 gene. These mutations were inherited from her parents. In the 20 normal individuals, these mutations were not identified. In the child, sex reversal may have been caused by CYP17A1 mutations. The compound heterozygous mutation of p. Thr101Ilefs*2 and p. Thr306Ale is a new gene mutation of 17α-hydroxylase/17, 20-lyase deficiency.

Waardenburg syndrome (WS) is an auditory-pigmentary disorder with varying combinations of sensorineural hearing loss and abnormal pigmentation. The present study aimed to investigate the underlying molecular pathology and provide a method of prenatal diagnosis of WS in Chinese families. A total of 11 patients with WS from five unrelated Chinese families were enrolled. A thorough clinical examination was performed on all participants. Furthermore, patients with WS underwent screening for mutations in the following genes: Paired box 3 (PAX3), melanogenesis associated transcription factor (MITF), SRY-box 10, snail family transcriptional repressor 2 and endothelin receptor type B using polymerase chain reaction sequencing. Array-based comparative genomic hybridization was used for specific patients whose sequence results were normal. Following identification of the genotype of the probands and their parents, prenatal genetic diagnosis was performed for family 01 and 05. According to the diagnostic criteria for WS, five cases were diagnosed as WS1, while the other six cases were WS2. Genetic analysis revealed three mutations, including a nonsense mutation PAX3 c.583C>T in family 01, a splice-site mutation MITF c.909G>A in family 03 and an in-frame deletion MITF c.649_651delGAA in family 05. To the best of the authors' knowledge the mutations (c.583C>T in PAX3 and c.909G>A in MITF) were reported for the first time in Chinese people. Mutations in the gene of interest were not identified in family 02 and 04. The prenatal genetic testing of the two fetuses was carried out and demonstrated that the two babies were normal. The results of the present study expanded the range of known genetic mutations in China. Identification of genetic mutations in these families provided an efficient way to understand the causes of WS and improved genetic counseling.

To analyze a child with facial abnormalities with combined cytogenetic and molecular techniques and delineate its clinical phenotype.Neuropsychological profile of the child was analyzed. Color Doppler, CT and MRI were used for detecting the nodules in the body. Conventional peripheral blood karyotypes of the child and his parents were analyzed with G-banding. Array-comparative genomic hybridization (aCGH) was performed to detect minor structural chromosomal abnormalities.The child had mental retardation, maxillofacial dysmorphism on the right side, and irregular solid nodules on the back. The karyotypes of the child and his parents were all normal, while aCGH has identified a de novo constitutive 1.2 Mb deletion at 17q11.2 in the child. The aCGH results of his parents were normal.The de novo 17q11.2 microdeletion probably underlies the facial abnormalities and neurofibromatosis in the patient.

To analyze a child with mental retardation, growth retardation and language development disorders.Conventional G-banding analysis was performed on chromosomes cultivated from peripheral blood samples derived from the child and her parents. Array-comparative genomic hybridization (aCGH) was performed to detect minor structural chromosomal abnormalities, and the result was confirmed by short tandem repeats (STR) analysis.For the child and her parents, no karyotypic abnormality was detected. However, aCGH analysis has identified a 14q22.1 deletion in the child. The microdeletion, with a size of 2.9 Mb was confirmed by STR analysis.The 2.9 Mb chromosomal microdeletion probably underlies the mental retardation, growth retardation and language development disorders in the child.

To screen potential mutations of PRRT2 gene in a Chinese family affected with paroxysmal kinesigenic dyskinesia (PKD).Polymerase chain reaction, DNA sequencing and restriction endonuclaese analysis were used to analyze all members of the family.A heterozygous mutation c.649dupC was identified in the PRRT2 gene in all patients, while no similar mutation was found in healthy members from the family.The c.649dupC mutation of the PRRT2 gene probably underlies the PKD in this family. Prenatal diagnosis can reduce the risk for further birth of affected children for this family.

We screened 60 known genes which are involved in inherited cataract in a pregnant woman with a four-generation family history of autosomal dominant congenital nuclear cataract through next-generation sequencing (NGS) and identified a heterozygous mutation, c.508dupC (p.L170fs), in the major intrinsic protein (MIP) gene. This mutation results in a frame-shift in MIP and has not been previously reported. The correlation of the mutation with disease was validated by Sanger sequencing of DNA from the other affected or unaffected members of the family. Therefore, our data expand the mutation spectrum of MIP mutation, and suggest that NGS is an accurate, rapid, and cost-effective method in the genetic diagnosis of congenital nuclear cataract.

To determine the origin of chromosomal aberration for a girl with mental retardation and multiple congenital deformities.The karotypes of the girl and her parents were analyzed with routine G-banding .Their genomic DNA was also analyzed with array comparative genomic hybridization (aCGH). Short tandem repeats (STR) were used to confirm the results of aCGH.There were no karyotypic abnormality detected at cytogenetic level. aCGH identified a de novo 1.28 Mb deletion at 2p15-p16.1 in the girl. The results of the STR confirmed the deletion affected the maternal chromosome.The de novo interstitial 2p15-p16.1 deletion may cause the mental retardation and multiple congenital deformities. chr2:60.5-61.5 Mb may be the minimal common region of 2p15-p16.1 microdeletion syndrome.

To detect mutation of COL1A1 gene in a Chinese family affected with type I osteogenesis imperfecta (OI) and to provide prenatal diagnosis for a fetus at 17th gestational week.Polymerase chain reaction, DNA sequencing and restriction endonuclease analysis were used to verify the detected mutation among other members of the family and 100 healthy controls.No mutation has been detected in the COL1A2 gene in all of the subjects. A heterozygous mutation c.104-1GC was identified in the COL1A1 gene among all patients from this family. The same mutation was not found in other members from the family and the 100 healthy controls. The mutation was not found in the fetus, and was verified to be a new mutation according to the type I collagen mutation database.The c.104-1GC mutation of the COL1A1 gene probably underlies the type I osteogenesis imperfecta in this family. Under the premise of a clear genetic diagnosis, prenatal diagnosis may be provided to reduce the risk for the disease.

SummaryAnchorage of tissue cells to their physical environment is an obligate requirement for survival that is lost in mature hematopoietic and in transformed epithelial cells. Here we find that a lymphocyte lineage-restricted transcription factor, Aiolos, is frequently expressed in lung cancers and predicts markedly reduced patient survival. Aiolos decreases expression of a large set of adhesion-related genes, disrupting cell-cell and cell-matrix interactions. Aiolos also reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66Shc and blocking anoikis in vitro and in vivo. In lung cancer tissues and single cells, p66Shc expression inversely correlates with that of Aiolos. Together, these findings suggest that Aiolos functions as an epigenetic driver of lymphocyte mimicry in metastatic epithelial cancers.