Personalized health risk assessment based on single-cell RNA sequencing analysis of a male with 45, X/48, XYYY karyotype.

Numeric sex chromosome abnormalities are commonly associated with an increased cancer risk. Here, we report a 14-year-old boy with a rare mosaic 45, X/48, XYYY karyotype presenting with subtle dysmorphic features and relative height deficiency, requiring growth hormone therapy. As only 12 postnatal cases have been described so far with very limited follow-up data, to assess the proband's long-term prognosis, including cancer risk, we performed high-throughput single-cell RNA sequencing (scRNA-seq) analysis.

Bilateral Ovarian Germ Cell Tumor in a 46,XX Female with Nijmegen Breakage Syndrome and Hypergonadotropic Hypogonadism.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, affecting mainly patients of Slavic origin. It is caused by a defect in the gene, resulting in defective nibrin protein formation. This leads to chromosomal instability, which predisposes to cancer, with lymphoid malignancies predominating.

Expression of BARD1 β Isoform in Selected Pediatric Tumors.

Currently, many new possible biomarkers and mechanisms are being searched and tested to analyse pathobiology of pediatric tumours for the development of new treatments. One such candidate molecular factor is (BRCA1 Associated RING Domain 1)-a tumour-suppressing gene involved in cell cycle control and genome stability, engaged in several types of adult-type tumours. The data on significance in childhood cancer is limited.

ALK alterations in salivary gland carcinomas.

Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells.

MAML2 rearrangement as a useful diagnostic marker discriminating between Warthin tumour and Warthin-like mucoepidermoid carcinoma.

Warthin tumour is the second most common benign neoplasm of salivary glands. Despite its relatively characteristic histology, it may sometimes mimic other lesions. Here, we report two female non-smoker patients diagnosed with low-grade mucoepidermoid carcinoma with oncocytic epithelium and prominent lymphoid (Warthin-like) stroma and with molecularly confirmed MAML2 rearrangement.

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer.

Gallbladder cancer (GBC) is a highly malignant tumor with poorly understood etiology. An insight into phenotypic features of this malignancy may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. We assessed the expression of female sex hormone receptors (ERα, ERβ, PR), connective tissue growth factor (CTGF) and HER2 in GBC, and adjacent normal tissue (NT), and determined their prognostic impact.

Clinical and Biological Significance of Gene Alteration and Estrogen Receptors Isoforms Expression in Breast Cancer Patients.

The amplification of estrogen receptor alpha (ERα) encoded by the gene has been described as having a prognostic role in breast cancer patients. However, increased dosage of the gene (tested by real-time PCR) is also observed in ER-negative breast cancers, which might suggest the expression of alternative isoforms of ERα (other than classical ERα of 66 kDa). In the current work, we have investigated the gene dosage in 402 primary breast cancer patients as well as the expression of ERα isoforms-ERα66 and ERα36-on mRNA and protein levels.

Application of high-resolution genomic profiling in the differential diagnosis of liposarcoma.

Background: Rarity and heterogeneity of liposarcomas (LPS) make their diagnosis difficult even for sarcoma-experts pathologists. The molecular mechanism underlying the development and progression of liposarcomas (LPS) remains only partially known. In order to identify and compare the genomic profiles, we analyzed array-based comparative genomic hybridization (array-CGH) profiles of 66 liposarcomas, including well-differentiated (WDLPS), dedifferentiated (DDLPS) and myxoid (MLPS) subtypes.

Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome, one of the most common human genomic syndromes, has highly heterogeneous clinical presentation. Patients usually harbor a 1.

Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype - retrospective analysis of Polish Adult Leukemia Group (PALG).

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK was performed. The impact of cladribine containing induction on treatment results was also evaluated.

[Probability rate of unbalanced offspring at birth and risk of unfavorable pregnancy outcomes in families of carriers of chromosomal reciprocal translocations involving chromosome 7].

Introduction: Carriership of reciprocal chromosomal translocation (RCT) may be the reason the occurrence of congenital malformations in the offspring, early neonatal death, stillbirth, and recurrent miscarriages due to unbalanced karyotype of gametes. The probability rate for individual categories of unfavorable outcomes depends on the kind of chromosome involved and is individually variable.

Objectives: The aim of study was to estimate the probability rates for unbalanced offspring and to evaluate the risk for different categories of unfavorable pregnancy outcomes, depending on the size of chromosomal segment with differentiation between maternal/paternal origin of the reciprocal chromosomal translocations involving chromosome 7p (RCT-7p) and 7q (RCT-7q).

On the significance of germline cytogenetic rearrangements at MYCN locus in neuroblastoma.

Background: MYCN oncogene amplification is the most important prognostic factor in neuroblastoma. 25% neuroblastoma tumors have somatic amplifications at this locus but little is known about its constitutional aberrations and their potential role in carcinogenesis. Here, we have performed an array-CGH and qPCR characterization of two patients with constitutional partial 2p trisomy including MYCN genomic region.

Different prognosis of acute myeloid leukemia harboring monosomal karyotype with total or partial monosomies determined by FISH: retrospective PALG study.

A monosomal karyotype (MK) was identified by banding techniques (BT) in acute myeloid leukemia (AML). However, BT may be insufficient to determine the actual loss of a complete chromosome, especially in complex karyotypes. We have investigated the effect of monosomy type, total (MK-t) and partial (MK-p), reevaluated by FISH, on prognosis.

Complex tumor-specific t(X;18) in seven synovial sarcoma tumors.

Cytogenetic analysis was performed of six monophasic synovial sarcomas (four primary, two recurrent tumors) and one recurrent poorly differentiated synovial sarcoma with complex tumor-specific t(X;18). In the complex translocations, besides chromosomes X and 18, the following chromosomes were involved: 1, 3, 5, 15, and 17. In all, taking these results together with findings of 20 previously published synovial sarcoma tumors with complex t(X;18), 13 different chromosomes were involved.

Bidirectionality and transcriptional activity of the EWSR1 promoter region.

EWSR1 is involved in chimeric proteins which play crucial roles in the development of a variety of bone and soft tissue tumors. Many of the chimeric genes involving EWSR1 have been extensively studied, whereas less is known about the wild-type (wt) gene and its regulation. As the expression of the chimeric gene is driven by the EWSR1 promoter, it is of importance to study the mechanisms regulating wt EWSR1 expression.

Prenatal diagnosis of an atrioventricular canal in a foetus with deletion of chromosome 8 (pter-->p21).

Congenital heart malformations, detected during a pregnancy, are associated in 20-48% of cases with a chromosomal aberration. In the following study we have reported the deletion of chromosome 8 (pter-->p21), diagnosed prenatally at 22 weeks of gestation, because of a visible defect in the upper part of the interventricular septum and a partial defect of the atrial septum. The atria and the ventricles were joined with a common central valve.

Periventricular heterotopia in a boy with interstitial deletion of chromosome 4p.

We report on a 4-year-old boy with a proximal interstitial deletion in the short arm of chromosome 4p with the karyotype 46,XY,del(4)(p14p15.32),inv(9)(p13q13). For a precise delineation of the deleted region, an array-based comparative genomic hybridization (a-CGH) analysis was performed.

A girl with duplication 9q34 syndrome.

We report on a 17-year-old female with numerous developmental abnormalities associated with 46,XX,dup(9)(q33.3q34.1), where the duplication occurred de novo.

Karyotypic characterization of 64 nonmalignant thyroid goiters.

Cytogenetic analyses were performed on 64 nonmalignant thyroid goiters (11 common and 53 multinodular goiters) after short-term culture. The majority of goiters (67%) were characterized by a normal karyotype, but in 5 common (45%) and 16 nodular (30%) goiters, small clones with various numerical and/or structural aberrations were found, in addition to many normal cells. Trisomy or tetrasomy 7 was the most frequent numerical aberration, seen in five cases.

Clinical impact of molecular and cytogenetic findings in synovial sarcoma.

Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene.

Spectral karyotyping reveals 17;22 fusions in a cytogenetically atypical dermatofibrosarcoma protuberans with a large marker chromosome as a sole abnormality.

The presence of an extra ring chromosome containing material from 17q and 22q, or, less frequently, a t(17;22)(q22;q13), is a cytogenetic hallmark of dermatofibrosarcoma protuberans (DFSP). However, occasionally tumors with other, atypical karyotypes are encountered. We describe a case of recurrent DFSP without a ring chromosome or a t(17;22) on standard cytogenetic analysis.

Identification of two U937 cell sublines exhibiting different patterns of response to tumour necrosis factor.

The monocytic cell line U937 is a frequently used model in studies on the cytotoxic effect of tumour necrosis factor (TNF). Two sublines of this cell line, termed U937(G) and U937(M), revealing different patterns of response to this cytokine, have been identified. The U937(G) cells, similarly to the cells obtained from ATCC, were resistant to the cytotoxic action of TNF in the absence of the protein-synthesis blocker cycloheximide (CHX).

Cytogenetics of hepatoblastoma: further characterization of 1q rearrangements by fluorescence in situ hybridization: an international collaborative study.

Background: Hepatoblastoma (HBT) is the most common hepatic neoplasm in children. This notwithstanding, little is known about pathogenetic factors, such as genetic abnormalities, of importance for the development and progression of this tumor type. To date, only 33 cytogenetically abnormal HBT have been published, and trisomies for chromosomes 2 and 20 have been shown to be the most frequent aberrations.