A Case Report of Verheij Syndrome.

Verheij syndrome (VRJS) is a rare genetic disorder characterized by a range of developmental issues and physical abnormalities. This condition is caused by mutations or deletions in the PUF60 (poly-U-binding factor 60 kDa) gene, which is located on the long arm of chromosome 8, specifically in the q24.3 region. We present a unique case of an 11-year-old girl child with VRJS. The child presented with absence seizures. She was noted to have short stature, spina bifida of the lower cervical vertebrae, and a smaller right kidney on ultrasonography. This case expands the phenotypic spectrum of VRJS by demonstrating a milder presentation, highlighting the importance of a high index of suspicion for the diagnosis, even in atypical presentations. Whole exome sequencing identified the causative mutation, confirming the diagnosis. Growth hormone therapy was initiated for short stature but discontinued due to the subsequent development of idiopathic intracranial hypertension. Additionally, this report represents the first documented case of VRJS in India, emphasizing the importance of global data sharing and collaboration for improving the understanding and management of rare genetic disorders.

Unraveling MYH9-related disease: A case study on misdiagnosis with idiopathic thrombocytopenic purpura, confirmed through genetic.

This paper presents a detailed analysis of a case initially misdiagnosed as Idiopathic Thrombocytopenic Purpura (ITP), which was later correctly identified as MYH9-related disease (MYH9-RD), a rare genetic disorder characterized by thrombocytopenia, large platelets, and Döhle-like inclusion bodies in neutrophils. Using advanced slide reading technology, our team identified hallmark features of MYH9-RD in the patient's blood samples, leading to genetic testing that confirmed a spontaneous mutation in the MYH9 gene. This report highlights the diagnostic journey, emphasizing the crucial role of recognizing specific hematologic signs to accurately diagnose MYH9-RD. By comparing our findings with existing literature, we highlight the genetic underpinnings and clinical manifestations of MYH9-RD, emphasizing the necessity for heightened awareness and diagnostic precision in clinical practice to prevent similar cases of misdiagnosis. This case demonstrates the importance of integrating genetic testing into routine diagnostic protocols for unexplained thrombocytopenia, paving the way for improved patient care and treatment outcomes.

Exploring the genetic basis of childhood monogenic diabetes.

Monogenic diabetes is caused by one or even more genetic variations, which may be uncommon yet have a significant influence and cause diabetes at an early age. Monogenic diabetes affects 1% to 5% of children, and early detection and genetically focused treatment of neonatal diabetes and maturity-onset diabetes of the young can significantly improve long-term health and well-being. The etiology of monogenic diabetes in childhood is primarily attributed to genetic variations affecting the regulatory genes responsible for beta-cell activity. In rare instances, mutations leading to severe insulin resistance can also result in the development of diabetes. Individuals diagnosed with specific types of monogenic diabetes, which are commonly found, can transition from insulin therapy to sulfonylureas, provided they maintain consistent regulation of their blood glucose levels. Scientists have successfully devised materials and methodologies to distinguish individuals with type 1 or 2 diabetes from those more prone to monogenic diabetes. Genetic screening with appropriate findings and interpretations is essential to establish a prognosis and to guide the choice of therapies and management of these interrelated ailments. This review aims to design a comprehensive literature summarizing genetic insights into monogenetic diabetes in children and adolescents as well as summarizing their diagnosis and management.

The roles of genetic mutation and cytokines/chemokines in immune response and their association with uveal melanoma patient outcome.

The impact of tumor mutations and the interplay of cytokines and chemokines on the immune response and clinical outcomes in uveal melanoma (UM) warrants further exploration. In our study, we delved into the correlation between genetic alterations and survival rates in a cohort of 188 UM patients, utilizing data from cBioPortal. We assessed the composition of immune cell populations within 80 UM tumors by examining RNA sequence-based gene expression data from The Cancer Genome Atlas (TCGA). Furthermore, we scrutinized the relationship between genetic mutations and the expression of cytokines and chemokines, as well as their influence on various immune cell subsets. Our investigation revealed a significant association between the presence of mutated GNAQ or SF3B1 genes and improved progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) when compared to patients with non-mutated counterparts. In contrast, the presence of immune response gene mutations was associated with a detrimental effect on PFS, DSS, and OS. We also observed that the expression levels of cytokines and chemokines were positively linked to the infiltration of immune killer cells and inversely related to the populations of B cells and dendritic cells. Elevated expression levels of PDCD1, TNF, IL6, CXCL9, and CXCL10 were found to be correlated with reduced OS. Intriguingly, an increase in CD8+ T cell populations was associated with a poorer OS, a finding that warrants further investigation. These findings underscore the potential utility of cytokines/chemokines expression levels, immune cell subsets, and mutation status as critical biomarkers for the selection of patients who are most likely to benefit from immunotherapeutic interventions. Our research provides valuable insights that could guide the development of more targeted and effective treatment strategies for UM patients.

Strategies for Identifying and Recruiting Women at High Risk for Breast Cancer for Research Outside of Clinical Settings: Observational Study.

BACKGROUND: Research is needed to understand and address barriers to risk management for women at high (≥20% lifetime) risk for breast cancer, but recruiting this population for research studies is challenging. OBJECTIVE: This paper compares a variety of recruitment strategies used for a cross-sectional, observational study of high-risk women. METHODS: Eligible participants were assigned female at birth, aged 25-85 years, English-speaking, living in the United States, and at high risk for breast cancer as defined by the American College of Radiology. Individuals were excluded if they had a personal history of breast cancer, prior bilateral mastectomy, medical contraindications for magnetic resonance imaging, or were not up-to-date on screening mammography per American College of Radiology guidelines. Participants were recruited from August 2020 to January 2021 using the following mechanisms: targeted Facebook advertisements, Twitter posts, ResearchMatch (a web-based research recruitment database), community partner promotions, paper flyers, and community outreach events. Interested individuals were directed to a secure website with eligibility screening questions. Participants self-reported method of recruitment during the eligibility screening. For each recruitment strategy, we calculated the rate of eligible respondents and completed surveys, costs per eligible participant, and participant demographics. RESULTS: We received 1566 unique responses to the eligibility screener. Participants most often reported recruitment via Facebook advertisements (724/1566, 46%) and ResearchMatch (646/1566, 41%). Community partner promotions resulted in the highest proportion of eligible respondents (24/46, 52%), while ResearchMatch had the lowest proportion of eligible respondents (73/646, 11%). Word of mouth was the most cost-effective recruitment strategy (US $4.66 per completed survey response) and paper flyers were the least cost-effective (US $1448.13 per completed survey response). The demographic characteristics of eligible respondents varied by recruitment strategy: Twitter posts and community outreach events resulted in the highest proportion of Hispanic or Latina women (1/4, 25% and 2/6, 33%, respectively), and community partner promotions resulted in the highest proportion of non-Hispanic Black women (4/24, 17%). CONCLUSIONS: Although recruitment strategies varied in their yield of study participants, results overall support the feasibility of identifying and recruiting women at high risk for breast cancer outside of clinical settings. Researchers must balance the associated costs and participant yield of various recruitment strategies in planning future studies focused on high-risk women.

Combined KRAS and TP53 mutation in patients with colorectal cancer enhance chemoresistance to promote postoperative recurrence and metastasis.

The response of patients with colorectal cancer to chemotherapy is tightly correlated with their genomic variation. Among these, APC, TP53, KRAS, PIK3CA are the most frequently mutated genes in advanced colorectal cancer patients. However, the precise correlation between these mutations and the therapeutic effects of chemotherapy remains elusive. Here, we conducted genome sequencing to identify commonly mutated genes in colorectal cancer patients and comprehensively assessed their sensitivity to chemotherapy drugs by monitoring computer tomography (CT) scans and carcinoembryonic antigen (CEA) levels. Surprisingly, we discovered that the objective response rate to the standard first-line chemotherapy among patients harboring combined KRAS and TP53 mutations is dismal, and these patients are predisposed to recurrence and metastasis. Furthermore, advanced-stage patients with concurrent KRAS and TP53 mutations are susceptible to developing cancer-associated cachexia due to chemotherapy resistance or forced cessation of treatment. Our findings underscore the urgent need for the development of innovative and novel chemotherapeutic strategies to effectively manage colorectal cancer patients harboring combined KRAS and TP53 mutations.

Neonatal Hyperekplexia: Is It Still a Diagnostic Challenge? Evidence From a Systematic Review.

Hyperekplexia is a neurologic disorder characterized by an exaggerated startle reflex in response to different types of stimuli. Hyperekplexia is defined by the triad of neonatal hypertonia, excessive startle reflexes, and generalized stiffness following the startle. Although uncommon, hyperekplexia can lead to serious consequences such as falls, brain injury, or sudden infant death syndrome.Aim of this study was to identify cases of neonatal hyperekplexia with a confirmed genetic diagnosis and to establish the genotype-phenotype correlation at onset. Articles were selected from 1993 to 2024 and PRISMA Statement was applied including newborns within 28 days of life. So, we retrieved from literature 14 cases of genetically confirmed neonatal hyperekplexia. The onset of clinical manifestations occurred in the first day of life in 8 of 14 patients (57.14%). Clinical findings were muscle stiffness (100%), startle reflex (66.66%), apnea/cyanosis (41.66%), positive nose-tapping test (33.33%), jerks (33.33%), jitteriness (25%), and ictal blinking (25%). Genes involved were GLRA1 in 9 of 14 (64.28%), SLC6A5 in 2 of 14 (14.28%), GPHN in 1 of 14 (7.14%), and GLRB in 2 of 14 (14.28%). Patients showed heterozygous (66.66%) or homozygous (33.33%) status. In 7 of 14 cases (50%), the condition occurred in other family members. A genotype-phenotype correlation was not achievable.Timely diagnosis is crucial to improve the natural history of hyperekplexia avoiding/reducing possible major complications such as sudden infant death syndrome, brain injury, and serious falls. Early differentiation from epilepsy minimizes treatment cost and improves the quality of life of patients.

Management of resistant and refractory cytomegalovirus infections after transplantation.

INTRODUCTION: Cytomegalovirus (CMV) is a classic opportunistic infection in transplant recipients. Treatment-refractory CMV infections are of concern, with growing identification of strains that have developed genetic mutations which confer resistance to standard antiviral therapy. Resistant and refractory CMV infections are associated with worse patient outcomes, prolonged hospitalization, and increased healthcare costs. AREAS COVERED: This article provides a comprehensive practical overview of resistant and refractory CMV infections in transplant recipients. We review the updated definitions for these infections, antiviral pharmacology, mechanisms of drug resistance, diagnostic workup, management strategies, and host-related factors including immune optimization. EXPERT OPINION: Resistant and refractory CMV infections are a significant contributor to post-transplant morbidity and mortality. This is likely the result of a combination of prolonged antiviral exposure and active viral replication in the setting of intensive pharmacologic immunosuppression. Successful control of resistant and refractory infections in transplant recipients requires a combination of immunomodulatory optimization and appropriate antiviral drug choice with sufficient treatment duration.

ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, neuronal excitability and NEK1 levels in human motor neurons.

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease leading to motor neuron loss. Currently mutations in > 40 genes have been linked to ALS, but the contribution of many genes and genetic mutations to the ALS pathogenic process remains poorly understood. Therefore, we first performed comparative interactome analyses of five recently discovered ALS-associated proteins (C21ORF2, KIF5A, NEK1, TBK1, and TUBA4A) which highlighted many novel binding partners, and both unique and shared interactors. The analysis further identified C21ORF2 as a strongly connected protein. The role of C21ORF2 in neurons and in the nervous system, and of ALS-associated C21ORF2 variants is largely unknown. Therefore, we combined human iPSC-derived motor neurons with other models and different molecular cell biological approaches to characterize the potential pathogenic effects of C21ORF2 mutations in ALS. First, our data show C21ORF2 expression in ALS-relevant mouse and human neurons, such as spinal and cortical motor neurons. Further, the prominent ALS-associated variant C21ORF2-V58L caused increased apoptosis in mouse neurons and movement defects in zebrafish embryos. iPSC-derived motor neurons from C21ORF2-V58L-ALS patients, but not isogenic controls, show increased apoptosis, and changes in DNA damage response, mitochondria and neuronal excitability. In addition, C21ORF2-V58L induced post-transcriptional downregulation of NEK1, an ALS-associated protein implicated in apoptosis and DDR. In all, our study defines the pathogenic molecular and cellular effects of ALS-associated C21ORF2 mutations and implicates impaired post-transcriptional regulation of NEK1 downstream of mutant C21ORF72 in ALS.

Congenital short bowel syndrome: Cases series in the same family and review of literature.

INTRODUCTION: Congenital short bowel syndrome (CSBS) is a rare congenital gastrointestinal disease and defined as a shortage of consecutive small bowel length present from birth. This syndrome is often accompanied by intestinal malrotation, reduction of peristalsis, and malabsorption. CASES PRESENTATION: This article reports on siblings carrying the Filamin A (FLNA) genetic mutation with CSBS The first case involved a child admitted to the hospital due to intestinal obstruction, undergoing four surgeries due to intestinal torsion with the remaining length of the small intestine only 60 cm, ultimately resulting in the child's death. The second case is a sibling of the first case, admitted to the hospital due to recurrent abdominal pain, diarrhea, and weight loss. With our previous experience, we conducted genetic testing for the filamin A gene (FLNA), revealing that both siblings and their mothers carried a mutation in the gene. CLINICAL DISCUSSION: The diagnosis can be indirectly based on the upper gastrointestinal tract contrast study, however, most of diagnoses are confirmed by exploratory surgery. There is no consensus on nutritional treatment guidelines for infants with congenital short-bowel syndrome. Bowel lengthening procedures have not been recommended for infants with CSBS. A lot of disease-causing mutations have been recorded as CXADR-like membrane protein (CLMP) and FLNA. CONCLUSION: Congenital short bowel syndrome is a rare condition with a poor prognosis. It requires multidisciplinary coordination for effective diagnosis and treatment. Ongoing research into genetic mutations like CLMP and FLNA is vital for understanding CSBS and enhancing patient care.

Fear of cancer recurrence in breast cancer survivors carrying a BRCA1 or 2 genetic mutation : a cross-sectional study.

BACKGROUND: Fear of cancer recurrence (FCR) affects virtually all patients who have been treated for cancer, to varying degrees. Breast cancer survivors who carry a BRCA1 or BRCA2 gene mutation are at high risk of cancer recurrence. No study has yet assessed FCR specifically in this population. OBJECTIVES: This cross-sectional study, conducted in women who were treated for breast cancer and carrying a BRCA1/2 mutation, aimed to: (1) assess the mean level of FCR and estimate the proportion of patients with clinical levels of FCR; (2) examine the relationships between FCR and selected psychological variables (e.g., avoidance, intolerance to uncertainty) and quality of life; (3) explore whether FCR levels vary as a function of the past preventive treatment received; and (4) to assess the associations between FCR and the presence of decisional conflict or regret regarding the various preventive options. METHOD: Participants were recruited through an e-mail sent to an oncogenetic network mailing list (Réseau ROSE). Participants were asked to complete a battery of questionnaires online assessing FCR and other psychological and quality of life variables. RESULTS: A total of 89 women completed the survey. Most participants had undergone a preventive mastectomy (62.9%) and a preventive salpingo-oophorectomy (75.3%) at the time of the study. The mean Fear of Cancer Recurrence Inventory-severity score was 16.8, which exceeds the clinical cut-off score of 13, and 70.8% of the participants showed a clinical level of FCR. FCR was significantly associated with higher levels of anxiety and depression, and higher avoidance and intolerance of uncertainty, but not with quality of life. No significant difference was observed on the total FCR score between women who had received preventive surgery (mastectomy and/or salpingo-oophorectomy) and those considering it, and those not considering it. The association was significant between higher FRC scores and greater decisional conflicts and regrets about choosing to undergo preventive surgery. CONCLUSION: These data suggest that FCR is a significant problem for breast cancer survivors carrying a BRCA1/2 genetic mutation, even after undergoing a prophylactic surgery. This highlights the importance of providing these women with specific psychological intervention focusing on FCR.

[Genetic Variation of SH2B3 in Patients with Myeloid Neoplasms].

OBJECTIVE: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms. METHODS: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed. RESULTS: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each. CONCLUSION: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

ß-N-methylamino-L-alanine production, photosynthesis and transcriptional expression in a possible mutation strain and a wild strain of Thalassiosira minima.

The neurotoxin ß-N-methylamino-L-alanine (BMAA) produced by marine diatoms has been implicated as an important environmental trigger of neurodegenerative diseases in humans. However, the biosynthesis mechanism of BMAA in marine diatoms is still unknown. In the present study, the strain of diatom Thalassiosira minima almost lost the biosynthesis ability for BMAA after a long-term subculture in our laboratory. The production of BMAA-containing proteins in the mutant strain of T. minima reduced to 18.2 % of that in the wild strain, meanwhile the cell size decreased but pigment content increased in the mutant strain. Take consideration of our previous transcriptional data on the mixed diatom and cyanobacterium cultures, the current transcriptome analysis showed four identical and highly correlated KEGG pathways associated with the accumulation of misfolded proteins in diatom, including ribosome, proteasome, SNARE interactions in vesicle transport, and protein processing in the endoplasmic reticulum. Analysis of amino acids and transcriptional information suggested that amino acid synthesis and degradation are associated with the biosynthesis of BMAA-containing proteins. In addition, a reduction in the precision of ubiquitination-mediated protein hydrolysis and vesicular transport by the COPII system will exacerbate the accumulation of BMAA-containing proteins in diatoms.

Advancements in the understanding and management of histiocytic neoplasms.

Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature. This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in high-risk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects. MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults. Further research is required to determine the optimal treatment duration and strategies for managing therapy interruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histiocytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

MASH as an emerging cause of hepatocellular carcinoma: current knowledge and future perspectives.

Hepatocellular carcinoma is one of the deadliest and fastest-growing cancers. Among HCC etiologies, metabolic dysfunction-associated fatty liver disease (MAFLD) has served as a major HCC driver due to its great potential for increasing cirrhosis. The obesogenic environment fosters a positive energy balance and results in a continuous rise of obesity and metabolic syndrome. However, it is difficult to understand how metabolic complications lead to the poor prognosis of liver diseases and which molecular mechanisms are underpinning MAFLD-driven HCC development. Thus, suitable preclinical models that recapitulate human etiologies are essentially required. Numerous preclinical models have been created but not many mimicked anthropometric measures and the course of disease progression shown in the patients. Here we review the literature on adipose tissues, liver-related HCC etiologies and recently discovered genetic mutation signatures found in MAFLD-driven HCC patients. We also critically review current rodent models suggested for MAFLD-driven HCC study.

Deep-GenMut: Automated genetic mutation classification in oncology: A deep learning comparative study.

Early cancer detection and treatment depend on the discovery of specific genes that cause cancer. The classification of genetic mutations was initially done manually. However, this process relies on pathologists and can be a time-consuming task. Therefore, to improve the precision of clinical interpretation, researchers have developed computational algorithms that leverage next-generation sequencing technologies for automated mutation analysis. This paper utilized four deep learning classification models with training collections of biomedical texts. These models comprise bidirectional encoder representations from transformers for Biomedical text mining (BioBERT), a specialized language model implemented for biological contexts. Impressive results in multiple tasks, including text classification, language inference, and question answering, can be obtained by simply adding an extra layer to the BioBERT model. Moreover, bidirectional encoder representations from transformers (BERT), long short-term memory (LSTM), and bidirectional LSTM (BiLSTM) have been leveraged to produce very good results in categorizing genetic mutations based on textual evidence. The dataset used in the work was created by Memorial Sloan Kettering Cancer Center (MSKCC), which contains several mutations. Furthermore, this dataset poses a major classification challenge in the Kaggle research prediction competitions. In carrying out the work, three challenges were identified: enormous text length, biased representation of the data, and repeated data instances. Based on the commonly used evaluation metrics, the experimental results show that the BioBERT model outperforms other models with an F1 score of 0.87 and 0.850 MCC, which can be considered as improved performance compared to similar results in the literature that have an F1 score of 0.70 achieved with the BERT model.

Autosomal Recessive Spastic Paraplegia and Psychomotor Retardation With or Without Seizures: A Case Report From Saudi Arabia.

Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) is a rare neurodevelopmental disorder associated with autosomal recessive mutations in the HACE1 gene. This case report presents the clinical features and genetic analysis of an 11-month-old girl and her sister with SPPRS, making it the third reported case in the Middle East and the second in Saudi Arabia. The patient exhibited hypotonia, global developmental delay, speech delay, swallowing difficulties, and recurrent respiratory infections. A homozygous pathogenic variant in the HACE1 gene (p.R664*) was identified through genetic analysis, confirming the diagnosis of SPPRS. This case report emphasizes the importance of considering variations in clinical presentation, especially in rare disorders where only a few cases are reported. Further research and case studies are needed to better understand the complete phenotypic spectrum of SPPRS and its complications.

Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.

Promising Therapeutic Targets for Recurrent/Metastatic Anaplastic Thyroid Cancer.

OPINION STATEMENT: Anaplastic thyroid cancer presents formidable challenges, particularly in cases of recurrence or metastasis. Timely BRAF V600E testing is imperative at diagnosis, initially through immunohistochemistry, followed by comprehensive genomic profiling encompassing genes such as NTRK, RET, ALK, and assessment of tumor mutation burden (TMB). FDA-approved treatment options include dabrafenib and trametinib for patients with BRAF mutations, while those exhibiting high TMB may benefit from pembrolizumab. Further therapeutic decisions hinge upon mutational profile, urgency of response required, airway integrity, and access to targeted therapies There is growing use of immunotherapy for ATC based on published reports of activity, but currently there is no FDA approved agent for ATC. The off-label utilization of "precision medicine" combinations imposes a considerable financial strain, underscoring the necessity for further clinical trials to elucidate promising therapeutic avenues for this orphan disease. There is a pressing need for the development and support of clinical trials investigating genomically driven and immune-based therapies for anaplastic thyroid cancer.