• Epigenetics
• genetics
• oncogenes
• retinoblastoma
• tumor suppressor gene

• PORTEC trials
• biomarker
• endometrial carcinoma
• p53 abnormal
• prognostic
• retinoblastoma protein

• Humans
• Female
• Endometrial Neoplasms/pathology
• Endometrial Neoplasms/genetics
• Endometrial Neoplasms/metabolism
• Retinoblastoma Protein/analysis
• Retinoblastoma Protein/genetics
• Tumor Suppressor Protein p53/genetics
• Middle Aged
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Aged
• Immunohistochemistry
• Adult
• Carcinoma, Endometrioid/pathology
• Carcinoma, Endometrioid/genetics
• Prognosis
• Aged, 80 and over
• Carcinosarcoma/pathology
• Carcinosarcoma/genetics
• Ubiquitin-Protein Ligases
• Retinoblastoma Binding Proteins

• CRPC
• gene mutation
• prostate cancer
• signaling pathway
• therapeutic targets

• Cell cycle
• Fertilization
• Plant gametes

• Cell Cycle/physiology
• Germ Cells, Plant/cytology
• Germ Cells, Plant/physiology
• Germ Cells, Plant/metabolism
• Cell Division/physiology
• Fertilization/physiology
• Signal Transduction

• PR00P3_201653 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

• Cancer
• Genetic variation
• Genetics
• Molecular genetics
• Ophthalmology

• Humans
• Retinoblastoma/genetics
• Retinoblastoma/pathology
• Retinoblastoma/diagnosis
• DNA Methylation/genetics
• Male
• Female
• Prognosis
• Epigenome/genetics
• Retinal Neoplasms/genetics
• Child, Preschool
• Infant
• Epigenomics/methods
• Child
• CpG Islands
• Alleles

• K08 EY033789 NEI NIH HHS
• P30 EY001730 NEI NIH HHS
• National Eye Institute
• Gerber Foundation
• Research to Prevent Blindness

• Cell Cycle/physiology
• Saccharomyces cerevisiae/genetics
• Saccharomyces cerevisiae/metabolism
• Saccharomyces cerevisiae/physiology
• Models, Biological
• Saccharomyces cerevisiae Proteins/metabolism
• Saccharomyces cerevisiae Proteins/genetics
• Transcription Factors/metabolism
• Transcription Factors/genetics
• DNA Replication
• Computational Biology
• Saccharomycetales/genetics
• Saccharomycetales/metabolism
• Saccharomycetales/physiology
• Cyclin-Dependent Kinases/metabolism
• Cyclin-Dependent Kinases/genetics
• Phosphorylation
• Repressor Proteins

• University of Colorado Anschutz start-up

• cellular senescence
• disease drivers of aging
• homeostasis
• progeria
• senolytics

• Humans
• Animals
• Mice
• Aging/physiology
• Cellular Senescence/physiology
• Disease Models, Animal
• Senescence-Associated Secretory Phenotype
• Homeostasis

• K12 GM133314 NIGMS NIH HHS
• American Federation for Aging Research
• 58-8050-9-004 Agricultural Research Service
• Agricultural Research Service
• American Federation for Aging Research

• Genetic testing
• N-myc
• RB1
• Retinoblastoma

• Humans
• Retinoblastoma/genetics
• Ophthalmology
• Retina
• Apoptosis
• Retinal Neoplasms/genetics

• The Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience

• PTEN
• cancer chemotherapy
• non-small cell lung cancer
• targeted therapy

• 671432 Elsa U. Pardee Foundation
• ES033806 National Institute of Health

• Humans
• Neoplasms/genetics

• R37 CA241486 NCI NIH HHS
• R37CA241486-01A1 NCI NIH HHS
• P50 CA211024-01A1 NCI NIH HHS
• NIH/NCI R25CA221738 NCI NIH HHS

• Humans
• Cell Differentiation/physiology
• Endoderm/metabolism
• Human Embryonic Stem Cells/metabolism
• Pluripotent Stem Cells/metabolism
• Retinoblastoma Protein/genetics
• Retinoblastoma-Like Protein p130/genetics

• Wellcome Trust
• G0701448 Medical Research Council
• European Research Council
• Cambridge Hospitals National Institute for Health Research Biomedical Research Center
• National Centre for the Replacement Refinement and Reduction of Animals in Research
• NC3Rs project grant and training fellowship
• Wellcome Trust and Medical Research Council - Cambridge Stem Cell Institute
• Japanese Society for the Promotion of Science

• cancer metabolism
• biochemistry

Less than 0.5% of intravenously injected drugs reach tumors, contributing to side effects. To limit damage to healthy cells, various delivery vectors have been formulated; yet, previously developed vectors suffer from poor penetration into solid tumors. This issue was resolved by the discovery of HN-1 peptide isolated via biopanning a phage-display library. HN-1 targets human head and neck squamous cell carcinoma (HNSCC) (breast, thyroid; potentially lung, cervix, uterine, colon cancer), translocates across the cell membrane, and efficiently infiltrates solid tumors. HN-1 peptide has been conjugated to various anticancer drugs and imaging agents though the identity of its receptor remained enigmatic.

To decipher the clues that pointed to retinoblastoma (Rb)-regulated discoidin-domain receptor 1 as the putative receptor for HN-1 is described.

HN-1 peptide was synthesized and purified using reverse-phase high-performance liquid chromatography and gel electrophoresis. The predicted mass was confirmed by mass spectroscopy. To image the 3-dimensional structure of HN-1 peptide, PyMOL was used. Molecular modeling was also performed with PEP-FOLD3 software via RPBS bioinformatics web portal (INSERM, France). The immunohistochemistry results of discoidin domain receptor 1 (DDR1) protein were obtained from the publicly accessible database in the Human Protein Atlas portal, which contained the images of immunohistochemically labeled human cancers and the corresponding normal tissues.

The clues that led to DDR1 involved in metastasis as the putative receptor mediating HN-1 endocytosis are the following: (1) HN-1 is internalized in phosphate-buffered saline and its uptake is competitively inhibited; (2) HN-1 (TSPLNIHNGQKL) exhibits similarity with a stretch of amino acids in alpha5 beta3 integrin (KLLITIHDRKEF). Aside from two identical residues (Ile-His) in the middle, the overall distribution of polar and nonpolar residues throughout the sequences is nearly identical. As HN-1 sequence lacks the Arg-Gly-Asp motif recognized by integrins, HN-1 may interact with an "integrin-like" molecule. The tertiary structure of both peptides showed similarity at the 3-dimensional level; (3) HN-1 is internalized by attached cells but not by suspended cells. As culture plates are typically coated with collagen, collagen-binding receptor (expressed by adherent but not suspended cells) may represent the receptor for HN-1; (4) DDR1 is highly expressed in head and neck cancer (or breast cancer) targeted by HN-1; (5) Upon activation by collagen, DDR1 becomes internalized and compartmentalized in endosomes consistent with the determination of ’energy-dependent clathrin-mediated endocytosis’ as the HN-1 entry route and the identification of HN-1 entrapped vesicles as endosomes; and (6) DDR1 is essential for the development of mammary glands consistent with the common embryonic lineage rationale used to identify breast cancer as an additional target of HN-1. In summary, collagen-activated tyrosine kinase receptor DDR1 overexpressed in HNSCC assumes a critical role in metastasis. Further studies are warranted to assess HN-1 peptide’s interaction with DDR1 and the therapeutic potential of treating metastatic cancer. Additionally, advances in delivery (conformation, endocytic mechanism, repertoire of targeted cancers of HN-1 peptide), tracking (HN-1 conjugated imaging agents), and activity (HN-1 conjugated therapeutic agents) are described.

The discovery of DDR1 as HN-1 peptide’s putative receptor represents a significant advance as it enables identification of metastatic cancers or clinical application of previously developed therapeutics to block metastasis.

• HN-1 peptide
• Solid tumor
• Targeted drug delivery
• Discoidin domain receptor 1
• Tyrosine kinase
• Metastasis

• RB1
• Retinoblastoma
• carrier
• genetics
• germline
• low-penetrance
• mutation

• CRISPR-Cas Systems
• Carcinogenesis/drug effects
• Carcinogenesis/genetics
• Carcinogens/pharmacology
• Cell Line
• Gene Knockout Techniques
• Genetic Predisposition to Disease/genetics
• Humans
• Mutation/genetics
• Neoplasms/genetics
• Neoplasms/pathology
• Oncogenes/genetics
• Retinoblastoma Binding Proteins/genetics
• Ubiquitin-Protein Ligases/genetics

• R21 CA171050 NCI NIH HHS
• R21 CA178529 NCI NIH HHS
• NIH

• cell cycle
• cellular differentiation
• pocket protein
• retinoblastoma
• therapeutic resistance
• tumor suppressor gene

• R25 GM095459 NIGMS NIH HHS
• National Institutes of Health

Rb1 is a regulator of cell cycle progression and genomic stability. This review focuses on post-translational modifications, their effect on Rb1 interactors, and their role in intracellular signaling in the context of cancer development. Finally, we highlight potential approaches to harness these post-translational modifications to design novel effective anticancer therapies.

The retinoblastoma protein (Rb1) is a prototypical tumor suppressor protein whose role was described more than 40 years ago. Together with p107 (also known as RBL1) and p130 (also known as RBL2), the Rb1 belongs to a family of structurally and functionally similar proteins that inhibits cell cycle progression. Given the central role of Rb1 in regulating proliferation, its expression or function is altered in most types of cancer. One of the mechanisms underlying Rb-mediated cell cycle inhibition is the binding and repression of E2F transcription factors, and these processes are dependent on Rb1 phosphorylation status. However, recent work shows that Rb1 is a convergent point of many pathways and thus the regulation of its function through post-translational modifications is more complex than initially expected. Moreover, depending on the context, downstream signaling can be both E2F-dependent and -independent. This review seeks to summarize the most recent research on Rb1 function and regulation and discuss potential avenues for the design of novel cancer therapies.

• cancer therapies
• cell cycle
• retinoblastoma

Since the discovery of the breast cancer susceptibility genes, BRCA1 and BRCA2, various other genes conferring an increased risk for breast cancer have been identified. Studies to evaluate sequence variants in cancer predisposition genes among women of African ancestry are limited and mostly focused on BRCA1 and BRCA2. To characterize germline sequence variants in cancer susceptibility genes, we analysed a cohort of 165 South African women of self-identified African ancestry diagnosed with breast cancer, who were unselected for family history of cancer. With the exception of four cases, all others were previously investigated for BRCA1 and BRCA2 deleterious variants, and were negative for pathogenic variants. We utilized the Illumina TruSight cancer panel for targeted sequencing of 94 cancer susceptibility genes. A total of 3.6% of patients carried a pathogenic/likely pathogenic variant in a known breast cancer susceptibility gene: 1.2% in BRCA1, 0.6% in each of BRCA2, ATM, CHEK2 and PALB, none of whom had any family history of breast cancer. The mean age of patients who carried deleterious variant in BRCA1/BRCA2 was 39 years and 8 months compared to 47 years and 3 months among women who carried a deleterious variant in other breast cancer susceptibility genes.

Few ideas in cancer genetics have been as influential as the “two-hit” theory of tumor suppressors. This idea was introduced in 1971 by Al Knudson in a paper in the Proceedings of the National Academy of Science and forms the basis for our current understanding of the role of mutations in cancer. In this theoretical discussion proposing a genetic basis for retinoblastoma, a childhood cancer of the retina, Knudson posited that these tumors arise from two inactivating mutations, targeting both alleles of a putative tumor suppressor gene. While this work built on earlier proposals that cancers are the result of mutations in more than one gene, it was the first to propose a plausible mechanism by which single genes that are affected by germ-line mutations in heritable cancers could also cause spontaneous, nonheritable tumors when mutated in somatic tissues. Remarkably, Knudson described the existence and properties of a retinoblastoma tumor suppressor gene a full 15 years before the gene was cloned.

• E2F family
• Helicobacter pylori
• RB-E2F pathway
• gastric cancer
• p53
• pocket protein

• RB protein
• biomarkers
• retinoblastoma
• treatments

• Leukocoria
• Neonatal retinoblastoma
• RB1
• Retinoblastoma

• mutational signature
• retinoblastoma
• structural rearrangement
• whole-genome sequencing

• 23916 Cancer Research UK
• C60100/A23916 Cancer Research UK
• Wellcome Trust
• C60100/A25274 Cancer Research UK

Mammalian development involves an exquisite choreography of cell division, differentiation, locomotion, programmed cell death, and senescence that directs the transformation of a single cell zygote to a mature organism containing on the order of 40 trillion cells in humans. How a single totipotent zygote undergoes the rapid stages of embryonic development to form over 200 different cell types is complex in the extreme and remains the focus of active research. Processes such as programmed cell death or apoptosis has long been known to occur during development to help sculpt organs and tissue systems. Other processes such as cellular senescence, long thought to only occur in pathologic states such as aging and tumorigenesis have been recently reported to play a vital role in development. In this review, we focus on apoptosis and senescence; the former as an integral mechanism that plays a critical role not only in mature organisms, but that is also essential in shaping mammalian development. The latter as a well-defined feature of aging for which some reports indicate a function in development. We will dissect the dual roles of major gene families, pathways such as Hox, Rb, p53, and epigenetic regulators such as the ING proteins in both early and the late stages and how they play antagonistic roles by increasing fitness and decreasing mortality early in life but contribute to deleterious effects and pathologies later in life.

• Hox proteins
• ING proteins
• apoptosis
• cancer
• development
• epigenetics
• retinoblastoma
• senescence

Lysine-specific histone demethylase 1 (LSD1) represents the first example of an identified nuclear protein with histone demethylase activity. In particular, it plays a special role in the epigenetic regulation of gene expression, as it removes methyl groups from mono- and dimethylated lysine 4 and/or lysine 9 on histone H3 (H3K4me1/2 and H3K9me1/2), behaving as a repressor or activator of gene expression, respectively. Moreover, it has been recently found to demethylate monomethylated and dimethylated lysine 20 in histone H4 and to contribute to the balance of several other methylated lysine residues in histone H3 (i.e., H3K27, H3K36, and H3K79). Furthermore, in recent years, a plethora of nonhistone proteins have been detected as targets of LSD1 activity, suggesting that this demethylase is a fundamental player in the regulation of multiple pathways triggered in several cellular processes, including cancer progression. In this review, we analyze the molecular mechanism by which LSD1 displays its dual effect on gene expression (related to the specific lysine target), placing final emphasis on the use of pharmacological inhibitors of its activity in future clinical studies to fight cancer.

Further research into the complex structure and behavior of an enzyme involved in gene regulation could improve future cancer therapies. The modification of chromosomal proteins known as histones can fundamentally change gene expression and influence the progression of diseases such as cancer. Bruno Perillo at the Italian National Research Council, Naples, Italy, and co-workers reviewed understanding of the structurally complex enzyme lysine-specific histone demethylase 1 A (LSD1), which interacts with multiple targets including histones. LSD1 removes methyl groups from histones, fine-tuning gene expression and influencing protein activity. The overexpression of LSD1 is linked to cancer development, particularly in aggressive cancers, and inhibiting LSD1 has shown promise in slowing progression and cancer spread. The researchers call for further research into the complexities of LSD1 activity, both in cancers and normal cell function.

A major advance was made to reduce the side effects of cancer therapy via the elucidation of the tumor-specific lytic path “hyperploid progression-mediated death” targeting retinoblastoma (Rb) or p53-mutants defective in G1 DNA damage checkpoint. The genetic basis of human cancers was uncovered through the cloning of the tumor suppressor Rb gene. It encodes a nuclear DNA-binding protein whose self-interaction is regulated by cyclin-dependent kinases. A 3D-structure of Rb dimer is shown, confirming its multimeric status. Rb assumes a central role in cell cycle regulation and the “Rb pathway” is universally inactivated in human cancers. Hyperploidy refers to a state in which cells contain one or more extra chromosomes. Hyperploid progression occurs due to continued cell-cycling without cytokinesis in G1 checkpoint-defective cancer cells. The evidence for the triggering of hyperploid progression-mediated death in RB-mutant human retinoblastoma cells is shown. Hence, the very genetic mutation that predisposes to cancer can be exploited to induce lethality. The discovery helped to establish the principle of targeted cytotoxic cancer therapy at the mechanistic level. By triggering the lytic path, targeted therapy with tumor specificity at the genetic level can be developed. It sets the stage for systematically eliminating side effects for cytotoxic cancer therapy.

• Retinoblastoma protein
• P53 protein
• Cancer
• Checkpoint
• Taxol
• Tumor-specific lytic path

Identifying patients with a genetic predisposition for developing malignant tumors has a significant impact on both the patient and family. Recognition of genetic predisposition, before diagnosing a malignant pathology, may lead to early diagnosis of a neoplasia. Recognition of a genetic predisposition syndrome after the diagnosis of neoplasia can result in a change of treatment plan, a specific follow-up of adverse treatment effects and, of course, a long-term follow-up focusing on the early detection of a second neoplasia.

Responsible for genetic syndromes that predispose individuals to malignant pathology are germline mutations. These mutations are present in all cells of conception, they can be inherited or can occur de novo.

Several mechanisms of inheritance are described: Mendelian autosomal dominant, Mendelian autosomal recessive, X-linked patterns, constitutional chromosomal abnormality and non-Mendelian inheritance.

In the following review we will present the most important genetic syndromes in pediatric oncology.

• genetic predisposition to disease
• genetic syndromes
• germ-line mutation
• pediatric cancer

• Animals
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• Humans
• Neoplasms/genetics
• Neoplasms/virology
• Oncogenes
• PTEN Phosphohydrolase/genetics
• Phosphatidylinositol 3-Kinase/genetics
• Phosphatidylinositol 3-Kinases/genetics
• Proto-Oncogene Proteins c-akt/genetics

• R35 CA220491 NCI NIH HHS

• RB1
• clinical features
• germline mutations
• large deletion/duplication
• retinoblastoma

• chemotherapy
• diagnostic testing
• eyeGENE®
• retinoblastoma

• DNA Mutational Analysis/methods
• Genes, Retinoblastoma/genetics
• Genotype
• Germ-Line Mutation/genetics
• High-Throughput Nucleotide Sequencing/methods
• Humans
• Mutation/genetics
• Phenotype
• Retina/pathology
• Retinal Neoplasms/genetics
• Retinoblastoma/genetics
• Retinoblastoma/pathology
• Retinoblastoma/therapy
• Retinoblastoma Protein/genetics

• P30 EY001583 NEI NIH HHS
• R01 EY023557 NEI NIH HHS
• K08CA232344 NCI NIH HHS
• 1RO1EY023557 NEI NIH HHS

The RB1 gene is the first described human tumor suppressor gene and plays an integral role in the development of retinoblastoma, a pediatric malignancy of the eye. Since its discovery, the stepwise characterization and cloning of RB1 have laid the foundation for numerous advances in the understanding of tumor suppressor genes, retinoblastoma tumorigenesis, and inheritance. Knowledge of RB1 led to a paradigm shift in the field of cancer genetics, including widespread acceptance of the concept of tumor suppressor genes, and has provided crucial diagnostic and prognostic information through genetic testing for patients affected by retinoblastoma. This article reviews the long history of RB1 gene research, characterization, and cloning, and also discusses recent advances in retinoblastoma genetics that have grown out of this foundational work.

• cancer genetics
• gene cloning
• genetic testing
• retinoblastoma
• tumor suppressor gene

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Cloning, Molecular
• Genes, Tumor Suppressor
• Humans
• Retinoblastoma/diagnosis
• Retinoblastoma/genetics
• Retinoblastoma Binding Proteins/genetics
• Retinoblastoma Binding Proteins/metabolism
• Ubiquitin-Protein Ligases/genetics
• Ubiquitin-Protein Ligases/metabolism

• K08 CA232344 NCI NIH HHS

• age-related macular degeneration
• comparative genomics
• inherited retinal degenerations
• photoreceptors
• proteomics
• redox-biology
• retinal development
• retinitis pigmentosa
• transcriptomics

• Animals
• Genomics/methods
• Humans
• Photoreceptor Cells/metabolism
• Photoreceptor Cells/pathology
• Proteome
• Retinal Degeneration/genetics
• Retinal Degeneration/metabolism
• Retinal Degeneration/pathology
• Transcriptome

• Complication
• Intra-arterial chemotherapy
• Intracameral chemotherapy
• Intravitreal chemotherapy
• Liquid biopsy
• Metastasis
• Retinoblastoma
• Treatment

• Breast cancer
• Disparity
• Genetic testing
• Precision medicine

Retinoblastoma, the most common primary intraocular malignancy of the young, is a prototype hereditary cancer. Due to its fairly predictable Mendelian inheritance, easily examinable tumors, and early age of presentation, RB has served as the most extensively studied model for genetics in cancer. The genetic strides in RB have progressed at an exponential rate since the 1970s. The highly morbid, reasonably curable and distinctly predictable inheritance pattern of RB; not to mention its propensity to affect our young, forms the basis of aggressively encouraging genetic diagnosis in all patients of RB. In this article, we present the basic and clinically relevant concepts of the genetics retinoblastoma.

• Genetic counselling
• MYCN mutation
• genetics of retinoblastoma

• MYCN
• cancer genetics
• neuroimaging
• optical coherence tomography
• pediatric cancer
• pineoblastoma

• Animals
• Child
• Humans
• Models, Animal
• Mutation
• Retinal Neoplasms/diagnostic imaging
• Retinal Neoplasms/genetics
• Retinal Neoplasms/pathology
• Retinal Neoplasms/therapy
• Retinoblastoma/diagnostic imaging
• Retinoblastoma/genetics
• Retinoblastoma/pathology
• Retinoblastoma/therapy

• R01 EY025641 NEI NIH HHS
• CIHR

• PTEN
• PTEN hamartoma tumor syndrome
• PTEN-opathies
• cancer risk assessment
• medical management
• molecular diagnosis

• Animals
• Endocrine System Diseases/genetics
• Humans
• Metabolic Diseases/genetics
• Mutation
• Neoplasms/genetics
• PTEN Phosphohydrolase/genetics
• Precision Medicine
• Syndrome

• RB1
• RNA-sequencing
• Retinoblastoma
• metabolic profiling
• non-coding RNA (LINC-RNA)
• tumor

• K22 CA204352 NCI NIH HHS
• P30 CA016058 NCI NIH HHS

• DNA, Neoplasm/analysis
• HLA-DQ Antigens/genetics
• Heterozygote
• Humans
• Melanoma/genetics
• Melanoma/immunology
• Polymorphism, Restriction Fragment Length

• Humans
• Hybrid Cells
• Multiple Endocrine Neoplasia/genetics
• Mutation
• Neoplasms/etiology
• Neoplasms/genetics
• Oncogenes
• Retinoblastoma/genetics
• Suppression, Genetic

• Breast Neoplasms/genetics
• Chromosome Deletion
• Female
• Gene Amplification
• Gene Rearrangement
• Genes, ras
• Humans
• Mutation
• Proto-Oncogenes
• Transfection

Retinoblastoma (RB) is an inherited childhood ocular cancer caused by mutations in the tumor suppressor RB1 gene. Identification of RB1 mutations is essential to assess the risk of developing retinoblastoma in the patients´ relatives. Retinoblastoma is a potentially curable cancer and an early diagnosis is critical for survival and eye preservation. Unilateral retinoblastoma is mostly non-heritable and results from two somatic mutations whereas bilateral retinoblastoma is heritable and results from one germline and one somatic mutation, both have high penetrance, 90%. The purpose of this study was to identify causative RB1 mutations in RB patients with different clinical presentations. A comprehensive approach was used to study a cohort of 34 patients with unilateral, bilateral and trilateral retinoblastoma. Blood and tumor DNA was analyzed by sequencing and multiplex ligation-dependent probe amplification (MLPA) assay. Validation of an insertion mutation was performed by cloning the PCR product. Most of the patients in our cohort had unilateral RB, eight patients had bilateral RB and one patient had a trilateral tumor with ocular and suprasellar/sellar locations. Other tumors in addition to retinoblastoma were also found in the affected families. One patient had two syndromes, retinoblastoma and schwannomatosis, and another RB patient had a father with a retinoma. Five out of the 25 unilateral RB patients carried germinal mutations (20%), which were mostly missense mutations. The bilateral and trilateral patients carried splice-site, nonsense and frameshift mutations as well as a whole RB1 gene deletion. Missense mutations were associated with mild phenotype: unilateral retinoblastoma, retinoma or no tumor. In this study we identified causative RB1 mutations in most bilateral RB patients and in some unilateral RB patients, including five novel mutations. These data are crucial for genetic counseling and confirm the need to perform complete genetic screening for RB1 mutations in both constitutional and tumor tissues.

• Argentina
• Base Pairing
• Base Sequence
• Child, Preschool
• Exons/genetics
• Female
• Genetic Counseling
• Heterozygote
• Humans
• Infant
• Infant, Newborn
• Male
• Mutation/genetics
• Pedigree
• Penetrance
• Retinoblastoma/genetics
• Retinoblastoma Protein/genetics
• Treatment Outcome

• Universidad de Buenos Aires

• CRISPR/Cas9
• cancer genome manipulation
• gene correction
• gene therapy
• oncogene disruption

Histone-modifying enzymes play a critical role in chromatin remodeling and are essential for influencing several genome processes such as gene expression and DNA repair, replication, and recombination. The discovery of lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, dramatically revolutionized research in the field of epigenetics. LSD1 plays a pivotal role in a wide range of biological operations, including development, cellular differentiation, embryonic pluripotency, and disease (for example, cancer). This mini-review focuses on the role of LSD1 in chromatin regulatory complexes, its involvement in epigenetic changes throughout development, and its importance in physiological and pathological processes.

• KDM1a
• LSD1
• cancer
• epigenetics
• histone demethylation