Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls.

Introduction: Long non-coding ribonucleic acids (lncRNAs) are involved in the cellular damage response following exposure to ionizing radiation as applied in radiotherapy. However, the role of lncRNAs in radiation response concerning intrinsic susceptibility to late effects of radiation exposure has not been examined in general or in long-term survivors of childhood cancer with and without potentially radiotherapy-related second primary cancers, in particular.

Methods: Primary skin fibroblasts (n=52 each) of long-term childhood cancer survivors with a first primary cancer only (N1), at least one second primary neoplasm (N2+), as well as tumor-free controls (N0) from the KiKme case-control study were matched by sex, age, and additionally by year of diagnosis and entity of the first primary cancer.

Radiation-response in primary fibroblasts of long-term survivors of childhood cancer with and without second primary neoplasms: the KiKme study.

Background: The etiology and most risk factors for a sporadic first primary neoplasm in childhood or subsequent second primary neoplasms are still unknown. One established causal factor for therapy-associated second primary neoplasms is the exposure to ionizing radiation during radiation therapy as a mainstay of cancer treatment. Second primary neoplasms occur in 8% of all cancer survivors within 30 years after the first diagnosis in Germany, but the underlying factors for intrinsic susceptibilities have not yet been clarified.

Identification of Genetic Predispositions Related to Ionizing Radiation in Primary Human Skin Fibroblasts From Survivors of Childhood and Second Primary Cancer as Well as Cancer-Free Controls: Protocol for the Nested Case-Control Study KiKme.

Background: Therapy for a first primary neoplasm (FPN) in childhood with high doses of ionizing radiation is an established risk factor for second primary neoplasms (SPN). An association between exposure to low doses and childhood cancer is also suggested; however, results are inconsistent. As only subgroups of children with FPNs develop SPNs, an interaction between radiation, genetic, and other risk factors is presumed to influence cancer development.

Δ133p53α enhances metabolic and cellular fitness of TCR-engineered T cells and promotes superior antitumor immunity.

Background: Tumor microenvironment-associated T cell senescence is a key limiting factor for durable effective cancer immunotherapy. A few studies have demonstrated the critical role of the tumor suppressor TP53-derived p53 isoforms in cellular senescence process of non-immune cells. However, their role in lymphocytes, in particular tumor-antigen (TA) specific T cells remain largely unexplored.

Correction to: Molecular karyotyping and gene expression analysis in childhood cancer patients.

The correct Author names are presented in this paper.

Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms.

The purpose of the present study was to investigate whether former childhood cancer patients who developed a subsequent secondary primary neoplasm (SPN) are characterized by elevated spontaneous chromosomal instability or cellular and chromosomal radiation sensitivity as surrogate markers of compromised DNA repair compared to childhood cancer patients with a first primary neoplasm (FPN) only or tumor-free controls. Primary skin fibroblasts were obtained in a nested case-control study including 23 patients with a pediatric FPN, 22 matched patients with a pediatric FPN and an SPN, and 22 matched tumor-free donors. Clonogenic cell survival and cytogenetic aberrations in Giemsa-stained first metaphases were assessed after X-irradiation in G1 or on prematurely condensed chromosomes of cells irradiated and analyzed in G2.

Homozygous variants in the gene SCAPER cause syndromic intellectual disability.

The S-Phase Cyclin A Associated Protein In The ER (SCAPER) gene is a ubiquitously expressed gene with unknown function in the brain. Recently, biallelic SCAPER variants were described in four patients from three families with retinitis pigmentosa (RP) and intellectual disability (ID). Here, we expand the spectrum of pathogenic variants in SCAPER and report on 10 further patients from four families with ID, RP, and additional dysmorphic features carrying homozygous variants in SCAPER.

CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development.

Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays.

CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in healthy tissue.

Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal.

Further evidence for pathogenicity of the TP53 tetramerization domain mutation p.Arg342Pro in Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a rare genetic disease with a highly significant predisposition to multiple early-onset neoplasms. These neoplasms include adrenocortical carcinoma, sarcoma, leukemia and CNS tumors in children and sarcoma, breast cancer and lung cancer in adults. LFS is inherited in an autosomal dominant manner.

Searching for gene expression differences in primary fibroblasts between patients with one and two neoplasms in childhood.

Genetic factors are important for developing primary and subsequent malignancies in children. This study investigated the role of genetic factors involved in DNA-repair. Designed as a feasibility study, it addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry.

The original family revisited after 37 years: odontoma-dysphagia syndrome is most likely caused by a microduplication of chromosome 11q13.3, including the FGF3 and FGF4 genes.

Objectives: Fibroblast growth factors consist of receptor tyrosine kinase binding proteins involved in growth, differentiation, and regeneration of a variety of tissues of the head and neck. Their role in the development of teeth has been documented, and their presence in human odontogenic cysts and tumors has previously been investigated. Odontoma–dysphagia syndrome (OMIM 164330) is a very rare disorder characterized by clustering of teeth as compound odontoma, dysplasia and aplasia of teeth, slight craniofacial abnormalities, and dysphagia.

Monozygotic twins discordant for constitutive BRCA1 promoter methylation, childhood cancer and secondary cancer.

We describe monozygotic twins discordant for childhood leukemia and secondary thyroid carcinoma. We used bisulfite pyrosequencing to compare the constitutive promoter methylation of BRCA1 and several other tumor suppressor genes in primary fibroblasts. The affected twin displayed an increased BRCA1 methylation (12%), compared with her sister (3%).

Reduced mRNA and protein expression of the genomic caretaker RAD9A in primary fibroblasts of individuals with childhood and independent second cancer.

Background: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.

Spatial learning and expression patterns of PP1 mRNA in mouse hippocampus.

Background: Synaptic plasticity is believed to be the major cellular basis for learning and memory. Protein phosphorylation is a key process involved in changes in the efficacy of neurotransmission. In long-term changes synaptic plasticity is followed by structural plasticity and protein de novo synthesis.

Unbalanced translocation 6p/16q (partial monosomy 6p and trisomy 16q): prenatal diagnosis and cytogenetics.

Unlabelled: Unbalanced translocation 6p/16q in one fetus is a very rare event and the prenatal sonographic findings have never been published before. We will give a short overview of the literature along with a case report focussing on prenatal ultrasound features and molecular cytogenetic analysis.

Case Description: A 21-year-old primigravid woman presented with a singleton pregnancy at 19 weeks' gestation.