PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Variant classification”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗
PubMed2002

Classifying the medulloblastoma: insights from morphology and molecular genetics.

Significant advances in the treatment of the medulloblastoma (MB) have been made in the last 30 years, reducing mortality by 2-fold. Further improvements in the cure rate require an increased understanding of the biology of MBs, and this will translate into refinements in their classification. Scrutiny of the cytological variation found among MBs has recently led to the concept of the anaplastic MB, which overlaps the large-cell variant and appears to share its poor prognosis. In contrast, the MB with extensive nodularity, a distinctive nodular/desmoplastic variant occurring in infants, has a better outcome than most MBs in these young patients. Building on cytogenetic studies that have drawn attention to abnormalities on chromosome 17 in over a third of MBs, research shows non-random losses on chromosomes 8, 9, 10, 11 and 16, and gains on chromosomes 1, 7 and 9. Overexpression of ErbB2 receptors and losses on chromosome 17p have been proposed as independent indicators of aggressive behaviour, while high TrkC receptor expression indicates a favourable outcome. There is a strong association between anaplastic/large-cell tumours and MYC amplification, which has previously been linked with aggressive disease, but associations between abnormalities on chromosome 17 and anaplastic/large-cell MBs and between abnormalities in the shh/PTCH pathway and the desmoplastic variant are more controversial. Classification of the MB histopathologically and according to profiles of molecular abnormalities will help both to rationalize approaches to therapy, increasing the cure rate and reducing long-term side-effects, and to suggest novel treatments.

Cerebellar Neoplasms↗
PubMed2004

Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.

The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms.

Adult↗
PubMedDate not supplied

Cecocolic torsion: classification, pathogenesis, and treatment.

Cecocolic torsion is a class of right colon obstruction. Under this heading, the known and the recently identified variants are unified under 1 classification. An algorithm is utilized to trace the pathogenesis of these variants. Recent data, prevailing definitions, and controversies are discussed and resolved. The significance of specific membranes and the blood supply is clarified. New symptoms, clinical and x-ray diagnoses are elucidated. The recommended treatments are outlined.

Algorithms↗
PubMed2001

Classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: a reappraisal of paraneoplastic pemphigus.

BACKGROUND: Recent studies suggest that paraneoplastic pemphigus (PNP) is a heterogeneous autoimmune syndrome involving several internal organs and that the pathophysiological mechanisms mediating cutaneous, mucosal, and internal lesions are not limited to autoantibodies targeting adhesion molecules. OBJECTIVE: To classify the diverse mucocutaneous and respiratory presentations of PNP and characterize the effectors of humoral and cellular autoimmunity mediating epithelial tissue damage. METHODS: We examined 3 patients manifesting the lichen planus pemphigoideslike subtype of PNP. A combination of standard immunohistochemical techniques, enzyme-linked immunosorbent assay with desmoglein (DSG) baculoproteins, and an immunoprecipitation assay were used to characterize effectors of humoral and cellular autoimmunity in patients with PNP and in neonatal wild-type and DSG3-knockout mice with PNP phenotype induced by passive transfer of patients' IgGs. RESULTS: In addition to the known "PNP antigenic complex," epithelial targets recognized by PNP antibodies included 240-, 150-, 130-, 95-, 80-, 70-, 66-, and 40/42-kd proteins but excluded DSG1 and DSG3. In addition to skin and the epithelium lining upper digestive and respiratory tract mucosa, deposits of autoantibodies were found in kidney, urinary bladder, and smooth as well as striated muscle. Autoreactive cellular cytotoxicity was mediated by CD8(+) cytotoxic T lymphocytes, CD56(+) natural killer cells, and CD68(+) monocytes/macrophages. Inducible nitric oxide synthase was visualized both in activated effectors of cellular cytotoxicity and their targets. Keratin 14-positive basal epithelial cells sloughed from the large airways and obstructed small airways. CONCLUSIONS: The paraneoplastic disease of epithelial adhesion known as PNP in fact represents only 1 manifestation of a heterogeneous autoimmune syndrome in which patients, in addition to small airway occlusion and deposition of autoantibodies in different organs, may display a spectrum of at least 5 different clinical and immunopathological mucocutaneous variants (ie, pemphiguslike, pemphigoidlike, erythema multiforme-like, graft-vs-host disease-like, and lichen planus-like). We suggest that the more encompassing term "paraneoplastic autoimmune multiorgan syndrome," or PAMS, be applied. The pathophysiological mechanisms of PAMS involve both humoral and cellular autoimmunity responses. Epithelial cell membrane antigens other than DSG1 or DSG3 are targeted by effectors of PAMS autoimmunity. Apoptosis of damaged basal cells mediates epithelial clefting, and respiratory failure results possibly from obstruction of small airways with sloughed epithelial cells.

Animals↗
PubMedDate not supplied

[The classification of nervous system tumors].

The paper presents the classification of tumors of the nervous system, which is based on the Second Variant of the International Histological Classification of Tumors of the Nervous System which was developed by the WHO experts in 1993 and on the section "Morphology of Neoplasms" of the International Classification of Diseases, Xth review. These classifications were critically reviewed by taking into account the experience gained by the Laboratory of Pathomorphology, Academician N. N. Burdenko Research Institute, Russian Academy of Medical Sciences. The proposed classification may unify the material of our country's neurosurgical clinics and provide more corrective statistic data.

Humans↗
PubMed1995

Phylogenetic position of Rickettsia tsutsugamushi and the relationship among its antigenic variants by analyses of 16S rRNA gene sequences.

The 16S rRNA gene sequences of Rickettsia tsutsugamushi and Rickettsia sibirica were determined by PCR and DNA sequencing. Phylogenetic analysis revealed that R. sibirica is positioned in a cluster of the genus Rickettsia with a similarity value of 98.1-99.6%, whereas R. tsutsugamushi is located apart from the cluster with a similarity value of 90.2-90.6%. This evidence suggests that R. tsutsugamushi should be excluded taxonomically from the genus Rickettsia. The phylogenetic classification of six antigenic variants in R. tsutsugamushi moderately reflected their antigenic relationship known in closely and distantly related strains.

Antigens, Bacterial↗
PubMedDate not supplied

Automated white blood cell classification revisited.

A novel approach to the problem of automated white blood cell classification is described. Whereas in most earlier attempts the segmentation of the cells has been recognized as the most difficult and most critical step in the sequence of operations resulting in the classification, the method described here eliminates the necessity of the detection of the contour of the nucleus and of the cytoplasm, and is therefore less sensitive to such disturbing factors as the presence of granules, of other cells touching the cell of interest, etc. The multiple sequential threshold method to be described here in two slightly different variants yields a correct classification rate of 94.7% for a 4 class problem (90 cells in the test set), and 91.8% for an 8 class problem (279 cells in the test set). Both experiments include immature cell types.

Densitometry↗
PubMed1985

[Comparative analysis of the histological variants of renal cell cancer].

85 cases of renal-cell carcinoma are studied histologically, cytologically and electron-microscopically. Morphological variant was determined according to the classification of N. A. Krayevsky et al. Histological and cytological variants of renal-cell carcinoma, differences of the degree of their differentiation are shown. Electron-microscopically the cell types characteristic of clear-cell and granular-cell variants of a different degree of differentiation are distinguished. Similarity of cell ultrastructure in granular-cell, sarcoma-like and glandular tumour variants is found. The ultrastructural features of nephrocytes and renal tubules in the form of the accumulation of microvilli, cytoplasmic membrane invaginations, desmosomes, basal membrane fragments which are seen as the markers of the tumour organospecificity were preserved in all variants of renal-cell carcinoma studied.

Adult↗
PubMed2001

Rapid molecular analysis of the haemagglutinin gene of human influenza A H3N2 viruses isolated in spain from 1996 to 2000.

A simple molecular technique was used for the rapid preliminary genetic characterization of human influenza A H3N2 viruses isolated in Spain from 1996 to 2000. Subtyping, based on RT-PCR, was followed by subtype-specific restriction enzyme fragment length polymorphism (RFLP) analyses of an amplified region of the HA1 domain of the H3 haemagglutinin (HA) gene to distinguish variants differentiated by common amino acid substitutions in HA1. The approach was tested using 135 Spanish H3N2 isolates and included nucleotide sequencing and phylogenetic analyses of a region of the HA1 domain of 41 representative isolates. The viruses were distinguished by haemagglutination inhibition (HI) assays into two antigenically discernible groups, the A/Wuhan/359/95-like and A/Sydney/5/97-like viruses. The results of PCR-RFLP analysis allowed a finer classification into five genetic variant subgroups, corresponding to those distinguished by phylogenetic analyses. This rapid, simple and variant-specific procedure could, therefore, be used to rapidly screen clinical specimens prior to more detailed antigenic and genetic analyses.

Hemagglutinin Glycoproteins, Influenza Virus↗
PubMed2000

[Hepatic arterial vascular anatomy and its variants].

PURPOSE: We investigated the frequency of anatomical variants of the hepatic artery, which can influence interventional angiographic procedures. MATERIAL AND METHODS: We reviewed 150 consecutive angiograms performed for the treatment of primary (112) or metastatic (38) liver tumors and evaluated the frequency of anatomical variants of the hepatic artery based on the classification proposed by Michels in 1955, which describes 10 variants. The so-called typical anatomy, which is in fact only found in 55% of cases, is indicated as type I. RESULTS: The typical anatomy (type I variant) was seen in 78 patients (52%) and variants were seen in the other 72 (48%). We found 15 type II variants (10%), 23 type III (15.5%), 1 type IV and 1 type V (0.6%), 3 type VI (2%), 1 type VII (0.6%) and finally 6 type IX (4%). There were no type VIII or X variants, but in 22 patients (14.7%) vascular anatomy did not fit Michaels' classification. DISCUSSION AND CONCLUSIONS: In our series the typical hepatic artery anatomy was found in 52%, which is in agreement with Michels' findings, while the frequency of the individual anatomical variants differed. Not all of the variants reported by Michels were seen in our series and we found 22 patients with different variants. Disagreement might be due to the fact that Michels' was an autoptic series while our patients were cancer patients only and thus variability could be at least partly accounted for by neoplastic neovascularization. We believe that thourough knowledge of the anatomical variants of the hepatic artery is fundamental to angiographic practice, in particular for interventional procedures, because such variants can influence the choice of vascular technique and of materials.

Angiography↗
PubMedDate not supplied

[Variants of hermaphroditism (clinical findings)].

False and true hermaphroditism (FH and TH) are often encountered in surgery for hypospadia. A clinically validated classification of various types and variants of hermaphroditism is proposed. FH is divided into male FH and female FH. TH also falls into two categories: TH without anomalies of external genitalia and that with these anomalies. The latter category has three variants: 1) all genitalia of males or females and some genitalia of the other sex; 2) some female and male organs in various combinations; 3) all organs of both sexes. All TH variants are illustrated by 5 case reports. These patients were thoroughly examined and their sex was surgically corrected.

Adolescent↗
PubMed2026

Genetic diversity and molecular mechanisms in hypertrophic cardiomyopathy: toward personalized therapy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac muscle disorder, yet contemporary genomic and mechanistic research still lacks a cohesive model explaining how diverse genetic architectures give rise to heterogeneous phenotypes. This review synthesizes advances across sarcomeric and nonsarcomeric mutations, including intermediate-effect variants, polygenic modifiers, and ancestry-dependent sources of variant misclassification to elucidate how these factors govern disease penetrance and clinical expression. It critically evaluates how genetic diversity intersects with key molecular pathways, including sarcomeric hypercontractility, calcium dysregulation, mitochondrial energy deficiency, and transforming growth factor-β (TGF-β) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling, to drive hypertrophic and fibrotic remodeling. Emerging mechanism-based therapies, such as myosin inhibition, allele-specific silencing, clustered regularly interspaced short palindromic repeats (CRISPR)-based correction, and metabolic modulation, are examined with respect to their capacity to modify upstream molecular drivers rather than downstream hemodynamic consequences. Persistent challenges, including variants of uncertain significance classification, ancestry-biased databases, inequitable access to genetic testing, and unresolved safety concerns for gene-based therapies, are critically assessed as major barriers to precision-medicine integration. By linking genetic architecture, molecular pathogenesis, and targeted interventions, this review advances a contemporary, mechanistically grounded framework that informs both individualized management and future research directions. Future research should prioritize pathway-specific therapeutics, functional and mechanistic validation of emerging variants, deeper physiologic phenotyping to refine disease modeling, and accelerate translation throughout the continuum of HCM pathophysiology.

Humans↗
PubMed2004

A harmonic structure of the genetic code.

In this paper is presented a new, very harmonic structure of the genetic code (GC) within a system of "4 x 5" (and/or of "5 x 4") of amino acids (AAs) in two variants. In first variant, the five rows within the system start with one polar charged amino acid (AA) each, making first column, consisting from five polar charged AAs (D, R, K, H, E). Five polar non-charged AAs (N, P, Y, W, Q) follow, then five non-polar AAs as last column (A, L, F, V, I) and, finally, five polar or non-polar AAs, in a combination, as first to last column (A as non-polar; S, T as polar, and G, P as ambivalent AAs). A second variant is subsequent to this one-"4 x 5" system with five nitrogen AAs (K, R, P, H, W), five oxygen (D, E, Y, S, T), five solely carbon (A, L, F, V, I) and five "combined" AAs (G with hydrogen as side chain; C and M with carbon and sulfur; N and Q with carbon, oxygen and nitrogen). A strict balance of atom and nucleon number as well as molecule mass follows the classification in both system variants.

Amino Acids↗
PubMed1994

[The current diagnosis of acute nonlymphoblastic leukemias].

The paper presents the results of the retrospective study of blast cells from 377 patients with acute nonlymphoblastic leukemia (ANLL). Morphocytochemical, immunological, cytogenetic assessments and cloning in semisolid agar were employed. The authors specify blast characteristics with reference to ANLL variants according to the FAB classification, define diagnostic criteria for poorly differentiated myeloblastic (MO), erythroblastic (M6) and megakaryoblastic (M7) leukemia, hybrid variants.

Adult↗
PubMed1983

Creatine kinase variants. Report on the workshop conference of the German Society for Clinical Chemistry held on September 19 to 21, 1982 in Tübingen, FRG.

It was the aim of the workshop to summarize present knowledge of the variant creatine kinases in human blood. Discussion was centered on the nature, measurement, and clinical significance of these variants. On the basis of the presented results, the different creatine kinase variants can be classified as follows: Normal size variants (80000 Daltons). These originate from postsynthetic modifications of the three dimeric isoenzymes creatine kinase-MM, MB or BB. The M subunit can be transformed by a serum constituent and these modifications result in at least three different creatine kinase-MM and two creatine kinase-MB variants, which still show catalytic activity. The mechanism of the postsynthetic alterations of creatine kinase-BB seems to be more complex: In vitro incubation of this isoenzyme even in a non-serum matrix changes its electrophoretic mobility and decreases activity. In vivo there is evidence that on the one hand intact creatine kinase-BB molecules are directly removed from the circulation. On the other hand, however, inactive creatine kinase-BB-protein is reported to occur in serum. Variants with higher molecular weights (greater than 200000 Daltons). These are termed macro creatine kinases. Macro creatine kinase type 1 comprises the immunoglobulin-bound creatine kinase isoenzymes. Of these immune complexes, IgG-linked creatine kinase-BB is well known and has been described in detail, whereas the occurrence of creatine kinase-MM-containing macro creatine kinases is still questionable. Macro creatine kinase type 1 is found in the blood of about 2% of all hospitalized patients. It occurs mainly in elderly women, but it is not known whether it has any special clinical significance. Macro creatine kinase type 2 is the term for an oligomeric form of mitochondrial creatine kinase released after breakdown of mitochondria in liver, heart and some tumours. After treatment with urea this oligomeric form is converted into a normal sized, dimeric creatine kinase-MiMi. Macro creatine kinase type 2 is found exclusively in seriously ill patients, and may occur in more than 3% of all hospitalized patients. This classification of the creatine kinase variants seems logical, since it takes into account the nature of the creatine kinase variants, and it permits the classification of all atypical creatine kinases described in the literature. As quantification and differentiation now become possible, further experimental and clinical investigations should provide the information necessary for a better understanding of the physiology and pathobiochemistry of these multiple forms of creatine kinase.

Creatine Kinase↗
PubMed1988

Malignant fibrous histiocytoma: the most common soft-tissue sarcoma.

Although soft-tissue sarcomas account for less than 1% of all malignancies, over 55 different histological variants have been described. Consequently clinicians often find the classification both complex and confusing. A new variant, the malignant fibrous histiocytoma (MFH), is now the most common adult soft-tissue sarcoma, therefore a clear understanding of the diagnosis, its implications and the optimum treatment is desirable.

Antineoplastic Combined Chemotherapy Protocols↗