Molecular Genetic Information Research Articles

Diagnosis and Risk Stratification of Acute Myeloid Leukemia, Myelodysplasia -Related

To analyze the clinical and genetic characteristics of acute myeloid leukemia, myelodysplasia-related (AML-MR) patients and evaluate their prognostic risk stratification, to guide clinical treatment decisions and improve understanding of the biological characteristics and disease progression. The study analyzed cellular and molecular genetic information of 307 AML-MR patients, diagnosed based on clinical history, bone marrow morphology, cytogenetics, and molecular genetic abnormalities. The risk stratification followed the 2022 ELN guidelines. 57 cases (18.6%) met the AML-MR diagnostic criteria based on morphology and clinical history, 110 cases (37.2%) met the AML-MR diagnostic criteria based on cytogenetic results, and 210 cases (74.5%) met the AML-MR diagnostic criteria based on molecular testing results. Among different type of mutations, ASXL1 mutation was the most frequent, followed by SRSF2 and BCOR mutations. Except for 2 cases with incomplete data that could not be classified, 263 (86.2%) of the 305 patients were classified as poor prognosis, 20 (6.6%) were classified as good prognosis group, and 22 (7.2%) were classified as intermediate prognosis group. Molecular genetic information plays a crucial role in diagnosing AML-MR, highlighting the importance of genetics in diagnosis and prognosis. Most AML-MR patients fall into poor prognosis categories, necessitating early intensive and targeted therapy for better survival outcomes.

Genetic Diversity, Kinship, and Polychromatism in the Spotted Eagle Ray Aetobatus ocellatus of Fiji

The spotted eagle ray Aetobatus ocellatus (Kuhl, 1923) has a widespread Indo-West Pacific distribution and displays substantial population genetic structuring. Genetic data are crucial for understanding the species’ diversity, connectivity, and adaptation. However, molecular genetic information on A. ocellatus from Melanesia is lacking, which impedes our understanding of gene flow among geographic regions. In this study, we sampled 45 A. ocellatus, primarily from Fiji’s largest fish market in the capital, Suva. Mitochondrial DNA Cytochrome C Oxidase subunit I (COI) barcoding was used for species identification, and DArT-seqTM technology was applied to assess the nuclear genetic diversity. Barcoding of the COI gene showed a 98.6% to 99.8% similarity to A. ocellatus reference sequences in the Barcode of Life Data System, and the 45 individuals were represented by three major evolutionary haplotype clusters. Genotyping resulted in 24,313 Single-Nucleotide Polymorphisms (SNPs) which were quality-filtered to 7094 SNPs per individual. The observed heterozygosity level was 0.310. The inbreeding coefficient was positive, and genotyping identified one full-sibling pair and one half-sibling pair from the 45 individuals. Additionally, eagle rays exhibit polychromatic patterns, and at least three ventral pattern variations were recorded in specimens from the market. Collectively, our main findings characterize the genetic profile of A. ocellatus in Fiji and can help to understand the diversification of this species within the region.

The genetic diversity and evolution analysis of the Hainan melioidosis outbreak strains

Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon “Dianmu” from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak.Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections.

Expression Patterns of TGF-β1, TβR-I, TβR-II, and Smad2 Reveal Insights into Heterosis for Growth of Hybrid Offspring between Acanthopagrus schlegelii and Pagrus major.

TGF-β1/Smads is a classic signaling pathway, which plays important roles in the development process of organisms. Black porgy Acanthopagrus schlegelii and red porgy Pagrus major are valuable economic fishes, and their hybrid offspring show excellent heterosis traits. Yet the molecular regulation mechanism of the heterosis traits is less clear. Here, we explored the TGF-β1/Smads pathway's molecular genetic information for heterosis in A. schlegelii ♂ × P. major ♀ (AP) and A. schlegelii ♀ × P. major ♂ (PA) in terms of growth and development. The mRNA expression levels of TGF-β1, TβR-I, TβR-II, and Smad2 genes in different developmental stages of A. schlegelii were detected. Furthermore, the expression levels of TGF-β1, TβR-I, TβR-II, and Smad2 genes in different tissues of adult (mRNA level) and larva (mRNA and protein level) of A. schlegelii, P. major, and their hybrids were determined by both real-time quantitative PCR and Western blot techniques. The results indicated the ubiquitous expression of these genes in all developmental stages of A. schlegelii and in all tested tissues of A. schlegelii, P. major, and its hybrids. Among them, the mRNA of TGF-β1, TβR-I, and TβR-II genes is highly expressed in the liver, gill, kidney, and muscle of black porgy, red porgy, and their hybrid offspring. There are significant changes in gene and protein expression levels in hybrid offspring, which indirectly reflect hybrid advantage. In addition, there was no correlation between protein and mRNA expression levels of Smad2 protein. The results provide novel data for the differential expression of growth and development genes between the reciprocal hybridization generation of black porgy and red porgy and its parents, which is conducive to further explaining the molecular regulation mechanism of heterosis in the growth and development of hybrid porgy.

Characterisation of glucose-induced protein fragments among the order Enterobacterales using matrix-assisted laser desorption ionization-time of flight mass spectrometry

To characterise the glucose-induced protein fragments by MALDI-TOF MS analysis, we compared data for samples from Escherichia coli cultured in media with or without glucose. Characteristic peaks were observed in the presence of glucose, and MS/MS revealed Asr-specific fragments. The amino acid sequences of the fragments suggested sequence-specific proteolysis. Blast-analysis revealed that numerous Enterobacterales harbored genes encoding Asr as well as E. coli. Here, we analysed 32 strains from 20 genera and 25 species of seven Enterobacterales families. We did not detect changes in the mass spectra of four strains of Morganellaceae lacking asr, whereas peaks of Asr-specific fragments were detected in the other 28 strains. We therefore concluded that the induction of Asr production in the presence of glucose is common among the Enterobacterales, except for certain Morganellaceae species. In members of family Budviciaceae, unfragmented Asr was detected. Molecular genetic information suggested that the amino acid sequences of Asr homologs are diverse, with fragments varying in number and size, indicating that Asr may serve as a discriminative biomarker for identifying Enterobacterales species.

Benefits and Pitfalls of Re-Operation for Recurrent Meningioma

Malignant forms of meningioma, such as atypical and anaplastic meningiomas, commonly relapse. Recently, there have been many reports elucidating the molecular biological mechanisms underlying meningioma recurrence. Tumors with loss of CDKN(cyclin dependent kinase)2A and 2B or lack of the tri-methylation of lysine 27 on histone H3 protein have a particularly high recurrence rate. In general, primary treatment for recurrent meningiomas comprises stereotactic radiosurgery(SRS)or stereotactic radiotherapy(SRT). However, re-operation is recommended for SRS-, SRT-refractory tumors. One of the benefits of reoperation is that it allows tumor control while decompressing the normal tissue, and changing the tumor microenvironment. Another is that it facilitates the acquisition of pathological and molecular genetic information, which can enable clinicians to recommend precision medicine. However, during reoperation, it is often difficult to detach the tumor from the surrounding brain tissue and cranial nerves because of severe adhesion. In cases of malignant meningiomas with multiple relapses, it is important to share the purpose and goal of the surgery with the patients and their families. In other words, which is being prioritized more, a high resection rate or functional outcomes? Furthermore, salvage surgery should also be a consideration.

HGG-26. MLH1, MSH2, MSH6, AND PMS2 IMMUNOHISTOCHEMISTRY REPRESENTS A HIGHLY SENSITIVE SCREENING METHOD FOR MISMATCH REPAIR DEFICIENCY SYNDROMES IN PEDIATRIC HIGH-GRADE GLIOMA

Abstract BACKGROUND Pediatric central nervous system (CNS) tumors can occur as first manifestations of cancer predisposition syndromes (CPS) resulting from pathogenic variants in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. Early detection of MMR deficiencies (MMRD) may warrant the therapeutic use of checkpoint inhibitors and enable genetic consulting for the patient’s families. METHODS We prospectively screened 128 pediatric high-grade gliomas (pedHGG) for MMR protein expression by immunohistochemistry (IHC) as part of the HIT-HGG-2013 clinical trial. We compared IHC results to independently collected patient information on CPS including MMRD to test the method’s efficiency in screening for Lynch syndrome and Constitutional MMRD syndrome CMMRD. RESULTS From 128 successfully tested tumors, ten cases (10/128, 7.8%), showed loss of expression of at least one of the MMR proteins. In seven of the ten affected patients (7/128, 5.5%), genetic testing uncovered heterozygous (6/10) or homozygous (1/10) pathogenic germline variants in MMR genes (MLH1, MSH2 or MSH6) confirming the diagnosis of Lynch syndrome respectively CMMRD. In three cases (3/128 2.3%), MMR alterations were restricted to tumor tissue. The group of diffuse midline gliomas, H3 K27-altered, (67/128, 52.3%) did not show MMR alterations, while either somatic or germline MMR mutations were detected in two of eight patients with diffuse hemispheric glioma, H3 G34-mutant. In 88 patients (88/128, 68.8%) either clinical or molecular-genetic information on CPS could be provided. All ten patients with signs of MMRD were successfully detected by IHC from tumor tissue. CONCLUSIONS IHC for MMR proteins represents a highly sensitive screening method for MMRD in pedHGG. Considering the occurrence of at least 11.5% (7/61) of MMRD in pediatric patients with diffuse high-grade glioma excluding DMG, MMRD IHC should be part of routine diagnostics as cost-effective, broadly available and robust screening method.

Updates from the International League Against Epilepsy Classification of Epilepsy (2017) and Focal Cortical Dysplasias (2022): Imaging Phenotype and Genetic Characterization.

The International League Against Epilepsy (ILAE) is an organization of 120 national chapters providing the most widely accepted and updated guidelines on epilepsy. In 2022, the ILAE Task Force revised the prior (2011) classification of focal cortical dysplasias to incorporate and update clinicopathologic and genetic information, with the aim to provide an objective classification scheme. New molecular-genetic information has led to the concept of "integrated diagnosis" on the same lines as brain tumors, with a multilayered diagnostic model providing a phenotype-genotype integration. Major changes in the new update were made to type II focal cortical dysplasias, apart from identification of new entities, such as mild malformations of cortical development and cortical malformation with oligodendroglial hyperplasia. No major changes were made to type I and III focal cortical dysplasias, given the lack of significant new genetic information. This review provides the latest update on changes to the classification of focal cortical dysplasias with discussion about the new entities. The ILAE in 2017 updated the classification of seizure and epilepsy with 3 levels of diagnosis, including seizure type, epilepsy type, and epilepsy syndrome, which are also briefly discussed here.

A rare case of TFEB/6p21/VEGFA-amplified renal cell carcinoma diagnosed by whole-exome sequencing: clinicopathological and genetic feature report and literature review

BackgroundTFEB/6p21/VEGFA-amplified renal cell carcinoma (RCC) is rare and difficult to diagnose, with diverse histological patterns and immunohistochemical and poorly defined molecular genetic characteristics.Case presentationWe report a case of a 63-year-old male admitted in 2017 with complex histomorphology, three morphological features of clear cell, eosinophilic and papillary RCC and resembling areas of glomerular and tubular formation. The immunophenotype also showed a mixture of CD10 and P504s. RCC with a high suspicion of collision tumors was indicated according to the 2014 WHO classification system; no precise diagnosis was possible. The patient was diagnosed at a different hospital with poorly differentiated lung squamous cell carcinoma one year after RCC surgery. We exploited molecular technology advances to retrospectively investigate the patient’s molecular genetic alterations by whole-exome sequencing. The results revealed a 6p21 amplification in VEGFA and TFEB gene acquisition absent in other RCC subtypes. Clear cell, papillary, chromophobe, TFE3-translocation, eosinophilic solid and cystic RCC were excluded. Strong TFEB and Melan-A protein positivity prompted rediagnosis as TFEB/6p21/VEGFA-amplified RCC as per 2022 WHO classification. TMB-L (low tumor mutational load), CCND3 gene acquisition and MRE11A and ATM gene deletion mutations indicated sensitivity to PD-1/PD-L1 inhibitor combinations and the FDA-approved targeted agents Niraparib (Grade C), Olaparib (Grade C), Rucaparib (Grade C) and Talazoparib (Class C). GO (Gene Ontology) and KEGG enrichment analyses revealed major mutations and abnormal CNVs in genes involved in biological processes such as the TGF-β, Hippo, E-cadherin, lysosomal biogenesis and autophagy signaling pathways, biofilm synthesis cell adhesion substance metabolism regulation and others. We compared TFEB/6p21/VEGFA-amplified with TFEB-translocated RCC; significant differences in disease onset age, histological patterns, pathological stages, clinical prognoses, and genetic characteristics were revealed.ConclusionWe clarified the patient’s challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.

Clinical and molecular characterization of patients with YWHAG-related epilepsy.

YWHAG variant alleles have been associated with a rare disease trait whose clinical synopsis includes an early onset epileptic encephalopathy with predominantly myoclonic seizures, developmental delay/intellectual disability, and facial dysmorphisms. Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG-related epilepsy. We included in this study 24 patients, 21 new and three previously described, with pathogenic/likely pathogenic variants in YWHAG. We extended the analysis of clinical, electroencephalographic, brain magnetic resonance imaging, and molecular genetic information to 24 previously published patients. The phenotypic spectrum of YWHAG-related disorders ranges from mild developmental delay to developmental and epileptic encephalopathy (DEE). Epilepsy onset is in the first 2 years of life. Seizure freedom can be achieved in half of the patients (13/24, 54%). Intellectual disability (23/24, 96%), behavioral disorders (18/24, 75%), neurological signs (13/24, 54%), and dysmorphisms (6/24, 25%) are common. A genotype-phenotype correlation emerged, as DEE is more represented in patients with missense variants located in the ligand-binding domain than in those with truncating or missense variants in other domains (90% vs. 19%, p < .001). This study suggests that pathogenic YWHAG variants cause a wide range of clinical presentations with variable severity, ranging from mild developmental delay to DEE. In this allelic series, a genotype-phenotype correlation begins to emerge, potentially providing prognostic information for clinical management and genetic counseling.

Identification of Candidate Genes for Red-Eyed (Albinism) Domestic Guppies Using Genomic and Transcriptomic Analyses.

Guppies are small tropical fish with brightly colored bodies and variable tail shapes. There are two phenotypes of domestic guppy eye color: red and black. The wild type is black-eyed. The main object of this study was to identify candidate genes for the red-eyed phenotype in domestic guppies. We hope to provide molecular genetic information for the development of new domestic guppy strains. Additionally, the results also contribute to basic research concerning guppies. In this study, 121 domestic guppies were used for genomic analysis (GWAS), and 44 genes were identified. Furthermore, 21 domestic guppies were used for transcriptomic analysis, and 874 differentially expressed genes (DEGs) were identified, including 357 upregulated and 517 downregulated genes. Through GO and KEGG enrichment, we identified some important terms or pathways mainly related to melanin biosynthesis and ion transport. qRT-PCR was also performed to verify the differential expression levels of four important candidate genes (TYR, OCA2, SLC45A2, and SLC24A5) between red-eyed and black-eyed guppies. Based on the results of genomic and transcriptomic analyses, we propose that OCA2 is the most important candidate gene for the red-eyed phenotype in guppies.

A New Record of Panulirus homarus homarus (Panulirus spp.) from Malaysia Waters with its Molecular Phylogeny

Spiny lobsters Panulirus spp. of the family Palinuridae Latreille, 1802 occupies the shallow tropical and subtropical waters (&lt;100 m depth). These species are ubiquitous and abundant, yet knowledge of its range, biodiversity, and population abundance in Malaysia is limited. Panulirus homarus is listed as “Least Concern” along with other 11 species out of 21 spiny lobster species in the International Union for Conservation of Nature and Natural Resources (IUCN) red list in 2022. A total of five species were reported from Malaysia waters. Whilst, this study reports the sixth spiny lobster species, Panulirus homarus homarus, with morphology and molecular genetic information (Cytochrome oxidase I (COI) gene) provided. The p-distance within P. h. homarus was 0.2 – 0.6%, n = 12; between P. h. homarus with P. h. rubellus and P. homarus “Brown” was 6.4 – 6.8%, n = 12 and 0.8 – 3.3%, n = 12, respectively. Intra-species p-distance within Panulirus spp. was below 3%, while inter-species was above 10%. This validates the collected specimen as P. h. homarus and P. h. rubellus is the subspecies, but leaving P. h. “Brown” taxonomic status unclear. Thus, genetic information is important in solving many of these systematic and taxonomic problems, because often these species are difficult to distinguished based on morphological criteria. A key to all Panulirus spp. identified in Malaysia waters was constructed. This study updates the marine biodiversity list in Malaysia, where the acquisition of biological knowledge is vital to the protection of the world’s natural resources as well as to the sustainable management of spiny lobster fisheries.

T-cell lymphoma patient harboring BCL11B mutations had favorable overall survival.

Molecular genetics serve a critical role in constructing risk stratification for hematological malignancies, but T-cell lymphoma (TCL) still lacks molecular genetic information for supplement risk stratification in predicting the prognosis of TCL patients. In the present study, we characterized the mutation patterns of B-cell leukemia/lymphoma 11B gene (BCL11B) and its prognostic importance in TCL patients. BCL11B mutations were characterized based on the data from two datasets, one is from our clinical center (GDPH dataset, n=79) and the other is from COSMIC dataset (n=154). The overall mutation rate of BCL11B was 6.4% (15/233) in TCL, and there were no hotspot mutation sites in TCL. Among these mutations, the missense and splice site mutation were significantly prominent. Moreover, TCL patients harboring BCL11B mutations had a favorable overall survival (OS) in our center (GDPH dataset) (adjusted hazard ratio [HR]=.001, p=0.109), although there were not yet significantly statistical at this point. In addition, TCL patients harboring BCL11B mutation had a longer 5-year restricted mean survival time (RMST) than those without a BCL11B mutation (60vs. 32 months). Notably, BCL11B mutations were not associated with TCL entities having better prognosis. BCL11B mutations were associated with favorable clinical outcome for TCL patients; it might be considered as a novel biomarker for TCL prognostic stratification.

Relationship between Some Myostatin Variants and Meat Production Related Calving, Weaning and Muscularity Traits in Charolais Cattle.

The slaughter value of live cattle can be assessed during visual conformation scoring, as well as by examining different molecular genetic information, e.g., the myostatin gene, which can be responsible for muscle development. In this study, the F94L, Q204X, nt267, nt324 and nt414 alleles of the myostatin gene (MSTN) were examined in relation to birth weight (BIW), calving ease (CAE), 205-day weaning weight (CWW), muscle score of shoulder (MSS), muscle score of back (MSB), muscle score of thigh (MST), roundness score of thigh (RST), loin thickness score (LTS), and overall muscle development percentage (OMP) of Charolais weaned calves in Hungary. Multi-trait analysis of variance (GLM) and weighted linear regression analysis were used to process the data. Calves carrying the Q204X allele in the heterozygous form achieved approximately 0.14 points higher MSB, MST and LTS, and 1.2% higher OMP, and gained 8.56 kg more CWW than their counterparts not carrying the allele (p < 0.05). As for the F94L allele, there was a difference of 4.08 kg in CWW of the heterozygous animals, but this difference could not be proved statistically. The other alleles had no significant effect on the evaluated traits.

Abstract 5357: Estrogen receptor gene expression prediction from H&amp;E-stained whole slide images

Abstract Gene expression profiling (GEP) represents an important approach to inform breast cancer treatment. However, access to GEP involves challenges associated with cost, tissue transportation, and turn around time. In this work, we explore the prediction of estrogen receptor gene (ESR1) expression directly from images of hematoxylin and eosin (H&amp;E) stained, formalin-fixed paraffin-embedded (FFPE) breast cancer tissue. Since H&amp;E staining is a fast and inexpensive component of the standard tissue preparation in pathology, this approach is tissue preserving and requires no additional tissue processing. Our method uses a deep multiple instance learning approach to process cropped image patches from whole-slide images (WSI) into a numeric embedding vector summarizing the information in each patch. A gated attention mechanism then aggregates these embeddings into a single prediction for the WSI. We train and tune the model on a site-based split of The Cancer Genome Atlas (TCGA) BRCA dataset, and evaluate it on both a heldout split of TCGA (independent sites) and a separate dataset from a tertiary teaching hospital (TTH). All splits of TCGA have ESR1 value, immunohistochemistry (IHC) estrogen receptor (ER) status, and limited clinical outcome data. The TTH dataset has IHC-based ER status and clinical outcome, but not ESR1 expression. On the TCGA heldout test split, our model’s root mean square error (RMSE) for predicting normalized gene expression counts (TPM) was 2.90 [95% CI: 2.57, 3.23], and the Pearson correlation was 0.57 [95%CI; 0.46, 0.67]. For predicting IHC-based ER status on the same TCGA split, this weakly-supervised ESR1-predicting model had an area under the receiver-operator curve (AUROC) of 0.81 [0.74, 0.87]. This was comparable to a strongly-supervised method directly predicting ER status (AUROC: 0.85 [0.77, 0.92]). Lastly, when evaluated for association with patient outcomes (progression-free interval; PFI) using the independent TTH dataset, this ESR1-predicting model had a concordance index (c-index) of 0.59 [0.52, 0.65]. For comparison, the c-index for PFI using the IHC-based ER status for these cases was 0.61 [0.54, 0.66]. This work further demonstrates the potential to infer gene expression from H&amp;E stained images in a manner that shows meaningful associations with clinical variables. Because obtaining H&amp;E stained images is substantially easier and faster than genetic testing, the capability to derive molecular genetic information from these images may increase access to this type of information for patient risk stratification and provide research insights into molecular-morphological associations. Future work incorporating more comprehensive sets of genes remains a valuable next step. Citation Format: Anvita A. Srinivas, Ronnachai Jaroensri, Ellery Wulczyn, James H. Wren, Elaine E. Thompson, Niels Olson, Fabien Beckers, Melissa Miao, Yun Liu, Cameron Chen, David F. Steiner. Estrogen receptor gene expression prediction from H&amp;E-stained whole slide images. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5357.

Deep Learning-Based Radiomics for Prognostic Stratification of Low-Grade Gliomas Using a Multiple-Gene Signature

Low-grade gliomas are a heterogeneous group of infiltrative neoplasms. Radiomics allows the characterization of phenotypes with high-throughput extraction of quantitative imaging features from radiologic images. Deep learning models, such as convolutional neural networks (CNNs), offer well-performing models and a simplified pipeline by automatic feature learning. In our study, MRI data were retrospectively obtained from The Cancer Imaging Archive (TCIA), which contains MR images for a subset of the LGG patients in The Cancer Genome Atlas (TCGA). Corresponding molecular genetics and clinical information were obtained from TCGA. Three genes included in the genetic signatures were WEE1, CRTAC1, and SEMA4G. A CNN-based deep learning model was used to classify patients into low and high-risk groups, with the median gene signature risk score as the cut-off value. The data were randomly split into training and test sets, with 61 patients in the training set and 20 in the test set. In the test set, models using T1 and T2 weighted images had an area under the receiver operating characteristic curve of 73% and 79%, respectively. In conclusion, we developed a CNN-based model to predict non-invasively the risk stratification provided by the prognostic gene signature in LGGs. Numerous previously discovered gene signatures and novel genetic identifiers that will be developed in the future may be utilized with this method.

Study of the Genetic Diversity of Some Wild Sunflower Species Using ISSR Markers

Wild sunflower species are adapted to diverse habitats and possess considerable variability for biotic and abiotic traits, therefore wild germplasm can be a real source for improving the narrow genetic base of the cultivated sunflower crop by introgression of new genes which were previously identified in wild genotypes. In order to effectively exploit these genes in cultivated genotypes, researchers need more information regarding the quantity and distribution of the genetic variability available within the wild sunflower species, which can offer a multitudine of valuable traits for traditional or molecular breeding. This study was conducted to reveal the genetic diversity of wild and cultivated sunflower genotypes using ISSR markers. From a total of 19 ISSR markers, which were used to evaluate the genetic diversity, eight markers (UBC808, UBC823, UBC834, UBC836, UBC840, UBC845, UBC853, 17899A) clearly differentiated the wild sunflower genotypes from the wild sunflower and/or the cultivated sunflower. The primers amplified a total of 120 alleles ranging from 10 to 22 alleles per marker. A wide range of fragment length was detected among the accessions, from 140 to over 1500 bp. The neighbor-joining dendrogram, based on Rogers genetic distance, of the genotypes studied consisted of two main clusters of different sizes: five entries were grouped into cluster A and the remaining six entries were grouped into cluster B. It is interesting that genotypes of Helianthus anuus L., Helianthus maximiliani and Helianthus argophyllus were clustered together. Another aspect observed, refers to interspecific variability for Helianthus debilis genotypes. Regarding the PCA, the first two principal axes accounted for 26.8% (CP1) and 16.1% (CP2) of the total variation, respectively, together explaining 42.9% of the total variability. In the future, this molecular genetic information can be combined with morphological and biochemical data to improve the sunflower breeding program.

STUDY OF GENETIC DIVERSITY IN PLUM GENOTYPES USING SRAP MARKERS

The hexaploid European plums (Prunus domestica L. and Prunus domestica subsp. insititia (L.) C.K.Schneid.) are main traditional fruit tree culture in Romania and represent an economically important fruit species with limited information on its genetic structure. Our objective was to fingerprint 33 cultivars using four Sequence-Related Amplified Polymorphism (SRAP) primer pairs to estimate the genetic relationships among local and international cultivars. The primer pairs amplified a total of 70 alleles ranging from 14 to 21 alleles per marker. A wide range of fragment length was detected among the accessions, from 65 to 2000 bp. The mean number of alleles per primer combination was 17.5, with the most alleles obtained with SRAP80 (21 alleles), range between 65-1800 bp and the fewest alleles (14) were obtained with SRAP95, range between 150-2000 bp. The neighbor-joining dendrogram, based on Rogers genetic distance, of the plum germplasm studied, consisted of two main clusters of different sizes: 23 entries were grouped into cluster 1 and the remaining 10 entries were grouped into cluster 2. It is interesting that cultivars representing plum species with 6x and 2x ploidy levels were clustered together. Another interesting aspect observed refers to plum genotypes clustered closely on the dendrogram according to their pedigree, such as 'Dani' (P14) - 'Tita' (P15), 'Roman' (P7) - 'Early Rivers' (P9), 'Zamfira' (P6) - 'Pescăruș' (P33). Accessions within the Romanian landrace/old autochthonous cultivars group were not clustered together. Regarding the PCA, the first two principal axes accounted for 12.91% (CP1) and 10.46% (CP2) of the total variation, respectively, together explaining 23.37% of the total variability. Our results showed that SRAP markers represent valuable tools for genetic diversity study on Prunus domestica. To our knowledge, this is the first study using SRAP markers for characterization of P. domestica germplasm. In the future, this molecular genetic information can be combined with phenological and biochemical data to identify genes, quantitative trait loci (QTL) and molecular markers that can be used to improve the plum crop breeding program.

Introduction

The 2021 WHO Classification of Central Nervous System tumors is a major advance in the field of neuro-oncology and neuropathology and represents a good example of translation of current molecular findings into a new classification system and more precise diagnostic criteria. Compared to the previous edition, in this fifth edition the integration of phenotypic and molecular genetic information in diagnostic categories has significatively increased. Moreover, the integration of epigenetic data through methylation profiling is the distinctive feature of this edition.&nbsp;In this issue of Pathologica, six review articles provide updates in the classification of major tumor categories relevant to diagnostic neuropathology according to the new WHO Classification. Antonelli and Poliani&nbsp;1 discuss the current classification of diffuse gliomas in adults, including the role of ancillary molecular testing in identifying distinct tumor types (e.g., EGFR amplification, TERT promoter mutation, and +7/10 in glioblastoma, IDH wildtype) and grading (homozygous CDKN2A/B homozygous deletion in IDH mutant astrocytomas)

Parametric Multispectral Mappings and Comparative Genomics

This article describes new algorithms that allow for viewing genetic sequences in the form of their multispectral images. We presented examples of the construction of such mappings with a demonstration of the practical problems of comparative genomics. New DNA visualization tools seem promising, thanks to their informativeness and representativeness. The research illustrates how a novel sort of multispectral mapping, based on decomposition in several parametric spaces, can be created for comparative genetics. This appears to be a crucial step in the investigation of the genetic coding phenomenon and in practical activities, such as forensics, genetic testing, genealogical analysis, etc. The article gives examples of multispectral parametric sets for various types of coordinate systems. We build mappings using binary sub-alphabets of purine/pyrimidine and keto/amino. We presented 2D and 3D renderings in different characteristic spaces: structural, integral, cyclic, spherical, and third-order spherical. This research is based on the method previously developed by the author for visualizing genetic information based on new molecular genetic algorithms. One of the types of mappings, namely two-dimensional, is an object of discrete geometry, a symmetrical square matrix of high dimension. The fundamental properties of symmetry, which are traced on these mappings, allow us to speak about the close connection between the phenomenon of genetic coding and symmetry when using the developed mathematical apparatus for representing large volumes of complexly organized molecular genetic information.