Key updates in the 2024 Edition of the International System for Human Cytogenomic Nomenclature (ISCN)

Congenital heart defects (CHD) are the leading cause of infant mortality, and are associated with chronic disability and morbidity in survivors. Most estimates of CHD prevalence are based on data from population-based birth defects surveillance systems. Considerable variability in the incidence of CHD was reported by a review of 44 international studies. Much of the variability appeared to be due to differences in the ascertainment of minor CHDs and the lack of a standardized classification system and nomenclature in prevalence studies. To derive an accurate estimate of the prevalence of CHD, this population-based study used a standardized cardiac nomenclature and classification system, the International Pediatric and Congenital Cardiac Code developed by members of the Society of Thoracic Surgeons and the European Association of Cardio-thoracic Surgery, to assess selected characteristics among infants with CHD identified in the Metropolitan Atlanta Congenital Defects Program (MACDP) from 1998 to 2005. The prevalence of CHD per 10,000 live births in the overall birth cohort was estimated. Infants with transient conditions such as patent ductus arteriosis that resolved in <6 weeks were excluded. Of the 398,140 live births in the cohort, 3240 had a CHD, for an overall prevalence of 81 infants/10,000 births. The most prevalent defects, comprising more than half of the total, were left-to-right shunt lesions. Of these, the most common defect was muscular ventricular septal defect, with a prevalence of 27.5/10,000 births. It occurred more than twice as often as the next two most common cardiac defects, perimembranous ventricular septal defect and secundum atrial septal defect, which occurred at a prevalence of 10.3 and 10.6/10,000 births, respectively. Other left-to-right-shunts found less frequently were atrial-ventricular septal defect and patent ductus arteriosus, with a prevalence of 4.1 and 2.9 /10,000 births, respectively. Among the cyanotic congenital heart defects, tetralogy of Fallot TOF was the most common, occurring in twice as many infants as transposition of the great arteries (4.7/10,000 births versus 2.3/10,000 births, respectively). Some CHD were associated with low gestational age and birthweight, older maternal age, multiple-gestation pregnancies, and infant gender. The investigators believe that current prevalence estimates of the various CHD subtypes provided in this study using standardized nomenclature and a well-documented classification system subtypes may be a benchmark for future studies.

As the field of cytogenetics and molecular genetics evolves, a standardized nomenclature system is critical for describing karyotypes and genomic changes accurately and concisely worldwide. The International System for Human Cytogenetic Nomenclature or ISCN is the communication tool for describing human chromosomes and chromosomal aberrations associated with human disease. This reference has served cytogeneticists since 1960, and through its periodic updates, it continues to provide standardized guidelines for consistency in the descriptive and interpretive reporting of the various chromosome aberrations observed in constitutional and neoplastic disorders. This chapter describes the general principles of the ISCN and offers guidance on writing abnormal cytogenetic results by providing nomenclature examples.

Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Specific chromosome rearrangements in different types of solid tumors have been described recently in a number of studies. However, the frequency and diagnostic importance of these chromosome rearrangements are currently under intensive investigation. The objective of this study is to provide a preliminary report on the types of clonal chromosome abnormalities observed in sarcomas of bone and soft tissues. Included in this report are osteosarcoma (five), synovial sarcoma (three), Ewing sarcoma (two), leiomyosarcoma (one), and spindle cell sarcoma (one). Cytogenetic analysis revealed clonal chromosome rearrangements in all of the tumors studied. Our findings correlated well with previously reported cytogenetic data on various types of solid tumors.

One of the challenges in epidemiologic studies of congenital heart defects (CHDs) has been the lack of a current, standard nomenclature and classification system. Recently such a standard nomenclature became available from the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database. This study reports the classification of cases of CHDs in a birth defects surveillance database using modified STS nomenclature. Records of infants and fetuses in the Metropolitan Atlanta Congenital Defects Program delivered during 1968-2003 with CHD diagnoses were reviewed by a team of pediatric cardiologists. The cases were assigned one or more STS codes and subsequently grouped into successively broader levels of aggregation. Aggregation was based on presumed morphogenetically similar developmental mechanisms. There were 12,639 cases reviewed, of which 89% had a single, primary STS code. Structural CHDs were found in 7,749 infants, while 4,890 were considered to have structurally normal hearts. Application of clinical CHD nomenclature improved the clinical accuracy of surveillance data by eliminating normal physiologic variants and obligatory shunt lesions. Classification also aggregated specific CHDs into groups appropriate for research and surveillance. Application of a current, standard CHD nomenclature and classification system to cases in a birth defects surveillance database improves the specificity of cardiac diagnoses and allows for the development of a flexible case aggregation system for monitoring of CHD prevalence.

Background. Developing a universal standardized microbial typing and nomenclature system that provides phylogenetic and epidemiological information in real time has never been as urgent in public health as it is today. We previously proposed to use genome similarity as the basis for immediate and precise typing and naming of individual organisms or viruses. In this study, we tested the validity of the proposed system and applied it to the epidemiology of infectious diseases using Ebola virus disease (EVD) outbreaks as the example. Methods. One hundred twenty-eight publicly available ebolavirus genomes were compared with each other, and average nucleotide identity (ANI) was calculated. The ANI was then used to assign unique codes, hereafter referred to as Life Identification Numbers (LINs), to every viral isolate, whereby each LIN consisted of a series of positions reflecting increasing genome similarity. Congruence of LINs with phylogenetic and epidemiological relationships was then determined. Results. Assigned LINs correlate with phylogeny at the species and infraspecies level and can even identify some individual transmission chains during the 2014-2015 EVD epidemic in West Africa. Conclusions. Life Identification Numbers can provide a fast, automated, standardized, and scalable approach to precisely identify and name viral isolates upon genome sequence submission, facilitating unambiguous communication during disease epidemics among clinicians, epidemiologists, and governments.

Background: Genome Mapping Technologies (optical and electronic) use ultra-high molecular weight DNA to detect structural variation and have application in constitutional genetic disorders, hematological neoplasms, and solid tumors. Genome mapping can detect balanced and unbalanced structural variation, copy number changes, and haplotypes. The technique is analogous to chromosomal microarray analysis, although genome mapping has the added benefit of being able to detect and ascertain the nature of more abnormalities in a single assay than array, karyotyping, or FISH alone. Key Messages: This paper describes a specific nomenclature for genome mapping that can be used by diagnostic and research centers to report their findings accurately. An international nomenclature is essential for patient results to be understood by different healthcare providers as well as for clear communication in publications and consistency in databases. Summary: Genome mapping can detect aneuploidy, balanced and unbalanced structural variation, as well as copy number changes. The Standing Committee for the International System for Human Cytogenomic Nomenclature (ISCN) recognised there was a need for a specific nomenclature for genome mapping that encompasses the range of abnormalities detected by this technique. This paper explains the general principles of the nomenclature as well as giving specific ISCN examples for the different types of numerical and structural rearrangements.

Taking Disclosure Seriously: Disclosing Financial Conflicts of Interest at the American College of Surgeons

The field of hair restoration surgery has experienced rapid growth and advancement, which has enabled an unparalleled aesthetic result compared to years past. Unfortunately, many of the recent advances and refinements have contributed to a concomitant increase in confusion regarding terminology. We submit that in order to critically perform accurate studies as well as relay pertinent information regarding techniques and outcomes, a standardized nomenclature system must be adopted. Such a system is described herein and terms are defined in a simple and precise manner. A standardized nomenclature system will enable the discipline of hair restoration surgery to move forward more efficiently and effectively by validating the field as a scientific discipline.

The genome of the domestic dog ( Canis familiaris ) is divided into 78 chromosomes, comprising 38 pairs of acrocentric autosomes and 2 metacentric sex chromosomes. Historically, the high degree of morphological similarity shared by many of the autosomes has presented significant challenges to cytogeneticists. Over the past decade, the development of reagents and resources for molecular cytogenetic analyses of the canine genome has played a vital role in the generation of comprehensive and effective genome and comparative maps for the dog. This chapter provides a summary of the molecular cytogenetic studies that have been conducted on the domestic dog, leading to the development of standardized chromosome nomenclature, comparative cytogenetic maps, integrated genome maps, and the anchoring of the canine genome assembly. The application of molecular cytogenetic approaches to the investigation of chromosome aberrations in canine cancers is also discussed. THE KARYOTYPE OF THE DOG The chromosome number of the dog, 2n = 78, was first determined from studies of meiotic cells (Minouchi 1928) and later confirmed using cultured lymphocytes (Gustavsson 1964). The diploid karyotype comprises 38 pairs of acrocentric autosomes, a large sub-metacentric X chromosome, and a small metacentric Y chromosome (Fig. 1). At approximately 137 Mb, the largest autosome, dog chromosome 1, is equivalent in size to human chromosomes 9–12, and all but the four largest dog chromosomes are smaller than human chromosome 19. Conventional Giemsa staining of the chromosomes allows precise identification of only the sex chromosomes (due to their size and morphology) and chromosome 1 (by virtue...

Infection of germline cells with retroviruses initiates permanent proviral colonization of the germline genome. The germline-integrated proviruses, called endogenous retroviruses (ERVs), are inherited to offspring in a Mendelian order and belong to the transposable element family. Endogenous retroviruses and other long terminal repeat retroelements constitute ~8% and ~10% of the human and mouse genomes, respectively. It is likely that each individual has a distinct genomic ERV profile. Recent studies have revealed that a substantial fraction of ERVs retains the coding potentials necessary for virion assembly and replication. There are several layers of potential mechanisms controlling ERV expression: intracellular transcription environment (e.g., transcription factor pool, splicing machinery, hormones), epigenetic status of the genome (e.g., proviral methylation, histone acetylation), profile of transcription regulatory elements on each ERV's promoter, and a range of stress signals (e.g., injury, infection, environment). Endogenous retroviruses may exert pathophysiologic effects by infection followed by random reintegration into the genome, by their gene products (e.g., envelope, superantigen), and by altering the expression of neighboring genes. Several studies have provided evidence that ERVs are associated with a range of pathogenic processes involving multiple sclerosis, systemic lupus erythematosus, breast cancer, and the response to burn injury. For instance, the proinflammatory properties of the human ERV-W envelope protein play a central role in demyelination of oligodendrocytes. As reviewed in this article, recent advances in ERV biology and mammalian genomics suggest that ERVs may have a profound influence on various pathogenic processes including the response to injury and infection. Understanding the roles of ERVs in the pathogenesis of injury and infection will broaden insights into the underlying mechanisms of systemic immune disorder and organ failure in these patients.

Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†☆

Proliferative epithelial lesions in the smaller caliber pancreatic ducts and ductules have been the subject of numerous morphologic, clinical, and genetic studies; however, a standard nomenclature and diagnostic criteria for classifying these lesion have not been established. To evaluate the uniformity of existing systems for grading duct lesions in the pancreas, 35 microscopic slides with 35 representative duct lesions were sent to eight expert pathologists from the United States, Canada, and Europe. Kappa values for interobserver agreement could not be calculated initially because more than 70 different diagnostic terms were used by the eight pathologists. In several cases, the diagnoses rendered for a single duct lesion ranged from "hyperplasia," to "metaplasia," to "dysplasia," to "carcinoma in situ." This review therefore demonstrated the need for a standard nomenclature and classification system. Subsequently, during a working group meeting, the pathologists agreed to adopt a single standard system. The terminology pancreatic intraepithelial neoplasia (or PanIN) was selected, and diagnostic criteria for each grade of PanIN were established (http://pathology.jhu.edu/pancreas_panin). This new system was then evaluated by having the eight pathologists rereview the original 35 cases. Only seven different diagnoses were rendered, and kappa values of 0.43, 0.14, and 0.42 were obtained for PanINs 1, 2, and 3 respectively. Cases assigned other diagnoses (e.g., squamous metaplasia) collectively had a kappa value of 0.41. These results show both the potential of the classification system, and also the difficulty of classifying these lesions even with a consistent nomenclature. However, even when there is lack of consensus, having a restricted set of descriptions and terms allows a better understanding of the reasons for disagreement. It is suggested that we adopt and apply this system uniformly, with continued study of its reliability and use, and possibly further refinement. The acceptance of a standard classification system will facilitate the study of pancreatic duct lesions, and will lead ultimately to a better understanding of their biologic importance.

The International Standing Committee on Human Cytogenomic Nomenclature (ISCN SC) considered feedback from the cytogenomics community to provide a more user friendly and organized presentation of general rules, improved example descriptions, more representative examples, and additional abbreviations. The ISCN 2024 edition represents one of the most significant reviews. Nomenclature for describing the findings of genomic mapping has been included for the first time. A key achievement of the Committee in preparing the ISCN 2024 is the provision of standardized nomenclature to ensure consistency in the ISCN description of findings irrespective of the cytogenomic technology used. This report highlights the main changes in the ISCN 2024 compared to previous editions and is a guide to assist in the transition to its implementation as the current nomenclature for describing cytogenomic findings.

A Standardized Nomenclature System for Head and Neck (H&N) IMRT Contouring, Planning and Quality Assurance