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[Prenatal diagnosis of women with an adverse reproductive history using both traditional karyotyping and SNP-array].

Objective: To explore the occurrence of fetal chromosomal abnormalities among pregnant women with an adverse reproductive history using trad … on/duplications (the sizes of duplications and deletions were between 422.4-1 708.4 kb) and 1 (1/4) loss of heterozygosity were detected by SNP-array, but were missed by karyotyping. Furthermore, 2 cases' copy number variation were found pathogenic gene related, while the other 2 were considered benign or variant of uncertain significance. Four cases (4/7) of abnormalit …

Identification and characterization of Birt-Hogg-Dubé associated renal carcinoma.

The Birt-Hogg-Dubé (BHD) gene is responsible for BHD syndrome, a rare autosomal dominant disease, characterized by benign hair follicle tumo … chitecture. In this tumour, both BHD alleles were inactivated by germline mutation concomitant with loss of heterozygosity, and the amount of BHD mRNA detected by real-time quantitative PCR (RQ-PCR) was very low. Renal tumour subtype/nephron segment-specific gene expression detected by RQ-PCR demonstrated that the tumour expressed relatively high amounts of alpha-methyl …

In Vitro Fertilization Using Preimplantation Genetic Testing in a Romanian Couple Carrier of Mutations in the TTN Gene: A Case Report and Literature Review.

Severe congenital myopathy with fatal cardiomyopathy (EOMFC) is a rare genetic neuromuscular disorder inherited in an autosomal recessive ma … aCGH + SNP analysis revealed an abnormal profile of the first newborn; three areas associated with loss of heterozygosity on chromosome 1 (q25.1-q25.3) of 6115 kb, 5 (p15.2-p15.1) of 2589 kb and 8 (q11.21-q11.23) of 4830 kb, a duplication of 1104 kb on chromosome 10 in the position q11.22, and duplication of 1193 kb on chromosome 16 in the position p11.2p11.1. Subseque …

BRIP1, a Gene Potentially Implicated in Familial Colorectal Cancer Type X.

Familial colorectal cancer Type X (FCCTX) comprises a heterogeneous group of families with an increased risk of developing colorectal cancer and other related tumors, but with mismatch repair-proficient, microsatellite-stable (MSS) tumors. Unfortunately, the genetic basis underlying their cancer predisposition remains unknown. Although pathogenic germline variants in BRIP1 increase the risk of developing hereditary ovarian cancer, the involvement of BRIP1 in hereditary colorectal cancer is still not well known. In order to identify new BRIP1 variants associated with inherited colorectal cancer

Evaluation of a Patient With Non-Myoinvasive Uterine Serous Carcinoma Confined to a Polyp and Positive Peritoneal Washings With Somatic ARHGAP35 and KRAS Mutations.

Currently, the application of peritoneal washings as a diagnostic tool for endometrial cancer staging is not well defined. The case describe … t DNA mismatch repair status, microsatellite stability, low tumor mutational burden (4 mut/Mb), low loss of heterozygosity (9%), amplification of the ERBB2 (HER2/neu) gene by both immunohistochemistry (3+, 20% positive) and fluorescence in-situ hybridization. Her tumor also had weakly positive estrogen receptor expression (1+, 10% positive); furthermore, some pathogenic …

Transcriptional alterations in hereditary and sporadic nonfunctioning pancreatic neuroendocrine tumors according to genotype.

BACKGROUND: Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associate … whereas some sporadic tumors clustered with MEN1. Four of 5 MEN1-like sporadic PanNET subtypes had loss of heterozygosity at the MEN1 gene locus. Pathway analysis demonstrated subtype-specific pathway activation, comprising angiogenesis and immune response in VHL; neuronal development in MEN1; protein ubiquitination in the new MEN1/sporadic subtype; and cytokinesis and …

AKT Inhibition in Solid Tumors With AKT1 Mutations.

Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and plasma cell-free DNA (cfDNA) were collected in the majori

Genomic Alterations In Primary Cardiac Diffuse Large B Cell Lymphoma: A Case Report And Literature Review.

Primary cardiac diffuse large B cell lymphoma (PC-DLBCL) is a rare kind of hematological malignancy, and its clinical and pathologic charact … 6p-, 6q-, 7q+, +11, 12q-, 15q-, 17q+, 17p-, +18, 19q+, 19p-, 19q-, X q+, and -Y and 4 copy-neutral loss of heterozygosity (CN-LOH) lesions located at 1q21.1q44, 3p26.3q11.2, 3q13.11q29 and 6p22.2p21.32 were identified by single nucleotide polymorphism (SNP) array karyotyping. Some key gene alterations in lymphoma, such as PRDM1 deletion and Bcl-2 amplification, were id …

Role of insulin-like growth factors in growth, development and feeding.

Information about the role of insulin-like growth factors (IGFs) is mainly derived from knockout (KO) and transgenic mice, human mutations in IGF1, IGF1R and IGFALS, and association studies with IGF1 SNPs. Igf1 KO mice show severely impaired pre- and postnatal growth and brain development and sensorineural hearing loss. Both local and endocrine IGF-1 are needed for normal growth. Igfals KO mice show a modest postnatal growth attenuation. Homozygous igf1r KO mice are severely growth impaired, while heterozygous mutations only show mild growth retardation. Two patients with a complete absence of

Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene-coding re…

SNP-Based Chromosomal Microarray Analysis in the Era of Optical Genome Mapping: An Enriched Case-Series Evaluating Copy-Neutral Events.

BACKGROUND/OBJECTIVES: Chromosomal microarray analysis (CMA) is an essential tool in modern cytogenetics for detecting copy number alterations and copy-neutral loss of heterozygosity (CN-LOH). As optical genome mapping (OGM) emerges as a potential replacement for traditional cytogenetic methods, the extent to which CMA remains necessary in routine diagnostic workflows remains to be elucidated. METHODS: We retrospectively reviewed 53 primary neoplastic cases, selected from a larger cohort of 327 hematologic malignancy specimens, in which CMA identified one or more CN-LOH events. Event size, ge…

Tumor profiling of advanced urothelial carcinoma: Comparative analysis based on social determinants of health.

BACKGROUND: Studies on the genomic characteristics of urothelial carcinoma (UC) patients from diverse backgrounds are scarce. Herein, we sou … e (P < 0.001) were seen in high ADI areas. There were no differences in microsatellite instability, loss of heterozygosity or PD-L1 expression. Patients from high ADI neighborhoods had lower TMB scores (62.7 % vs. 51.3%) when compared to low ADI neighborhoods (P = 0.291). The genes with higher rates of alterations when comparing low vs high ADI areas were PIK3CA (20.9% …

Comprehensive Immunogenomic Profiling of IDH1-/2-Altered Cholangiocarcinoma.

PURPOSE: Isocitrate dehydrogenase (IDH)1/2 genomic alterations (GA) occur in 20% of intrahepatic cholangiocarcinoma (iCCA); however, the immunogenomic landscape of IDH1-/2-mutated iCCA is largely unknown. METHODS: Comprehensive genomic profiling (CGP) was performed on 3,067 cases of advanced iCCA. Tumor mutational burden (TMB), PD-L1 expression (Dako 22C3), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) as a surrogate marker for homologous recombination deficiency were examined. RNA sequencing of 73 patient samples was analyzed for differences in stromal/immune ce…

Multimodule characterization of immune subgroups in intrahepatic cholangiocarcinoma reveals distinct therapeutic vulnerabilities.

BACKGROUND: Immune microenvironment is well recognized as a critical regulator across cancer types, despite its complex roles in different d … lammation-dominated immunosuppression. Although tumor mutation burden was relatively higher in IG2, loss of heterozygosity in human leucocyte antigen and defects in antigen presentation undermined the recognition of neoantigens, contributing to immune-exclusion behavior. Pathological analysis confirmed that tumor-infiltrating lymphocytes and tertiary lymphoid structures …

Prevalence of germline variants in USP8, USP48, CABLES1 and PAM in patients with pituitary adenomas.

OBJECTIVE: Approximately 5% of pituitary adenomas (PA) are familial, linked to germline variants in AIP, or syndrome-related genes like MEN1 … encies, in silico prediction and segregation analysis. We analyzed tumor DNA from 2 cases to assess loss of heterozygosity (LOH). RESULTS: Uncommon heterozygous germline variants were identified in 30 patients (9.2%), all clinically sporadic. Most variants were classified as benign or of uncertain significance (VUS). Several variants, including USP8 c.104+3A>G, USP48 p …

HRDetect in Tubo-ovarian Carcinoma: Stratification and Therapeutic Implications.

PURPOSE: To evaluate HRDetect, a mutational signature-based algorithm, for prognostic utility in tubo-ovarian carcinoma and to determine if … res were calculated using substitution signatures, RS, microhomology-mediated deletions, and global loss of heterozygosity. An independent validation cohort (ARIEL2, n = 77) of platinum-sensitive tubo-ovarian carcinoma treated with rucaparib was analyzed to correlate HRDetect with PARP inhibitor (PARPi) response. RS analysis and unsupervised hierarchical clustering were …

Talazoparib Monotherapy in Metastatic Castration-resistant Prostate Cancer with DNA Damage Response Alterations-Genomic Features Associated with Response to Therapy.

BACKGROUND AND OBJECTIVE: The impact of alterations beyond DNA damage response-homologous recombination repair (DDR-HRR) genes on outcomes w … lteration origin, selected non-DDR-HRR gene alteration status, tumor mutational burden, and genomic loss of heterozygosity (gLOH) were explored. Objective response rates (ORRs) and median overall survival (OS) with 95% confidence intervals (Clopper-Pearson method) and p values (two-sided Fisher's exact test) were calculated. Commonly altered non-DDR-HRR genes included T …

Characterization and identification of novel polymorphisms in the OR51H1 gene associated with resistance/tolerance to natural Theileria infection in Vechur (Bos indicus) and crossbred (B. taurus × B. indicus) cattle in a Theileria-endemic region.

Theileriosis is a haemo protozoan disease affecting livestock, causing high mortality and production loss. Although therapeutic and vector control measures are available, selecting Theileria-resistant/tolerant animals is considered an alternate control measure for which the identification of genetic markers is essential. The present study screened dwarf Vechur (Bos indicus) and crossbred (B. taurus × B. indicus) cattle for natural infection to Theileria using peripheral blood smear and clinical and haematology evaluation. Polymorphisms in a previously identified candidate gene were screened in

Natural history of hypophosphatasia in Chinese patients younger than 18 years: a single-center retrospective observational study.

PURPOSE: To summarize the clinical features, natural history, and ALPL variant spectrum of Chinese children with hypophosphatasia (HPP), and to evaluate diagnostic features across clinical subgroups. METHODS: This single-center retrospective observational study included children diagnosed with hypophosphatasia at our hospital who had not received enzyme replacement therapy. Published Chinese pediatric hypophosphatasia cases were also reviewed and combined with the single-center cohort for descriptive analyses. RESULTS: Ninety-two children were included in the pooled cohort, comprising 23 pat

Комплексный номер копий с высоким разрешением и гистомолекулярный анализ диффузной глиомы в масштабах полушария, H3 G34-mutant обнаруживает общие аномалии TP53.

Диффузная глиома в масштабах полушария, Н3 G34-mutant (В тыс.DHG-H3 G34 характеризуется главным образом молекулярным профилированием метилирования и исследованиями последовательности. Мы описываем комплексную гистомолекулярную оценку, включая профили копий с высоким разрешением серии 60 DHG-H3 G34 для дальнейшего понимания спектра генетических изменений, связанных с этим типом опухолей. Случаи были подвергнуты клиническому тестированию с использованием: 187-gene мутация и синтез были нацелены на нейроонтологию следующего поколения (n = 60) и онкосканского хромосомного микроаррара (n = 26) одно

Совпадение в аннотации оригинала
Diffuse hemispheric glioma, H3 G34-mutant (DHG-H3 G34) has been primarily molecularly characterized by methylation profiling and sequencing … ent copy number abnormalities were losses involving 3q, 4q, 10q, 13q, and 18q, and 17p copy-neutral loss of heterozygosity (cnLOH) encompassing TP53. This copy number profile was reminiscent of that seen in Grade 4 IDH-mutant astrocytomas. Collectively, a TP53 abnormality at copy number (12/26, all cnLOH), sequence (55/60) and protein expression (46/48) level was detect …