Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy.

Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices.

The Management of Oligoprogression in the Landscape of New Therapies for Metastatic Melanoma.

: A limited degree of progression after a response to treatment is labelled as oligoprogression and is a hot topic of metastatic melanoma (MM) management. Rogue progressive metastases could benefit from local treatment, which could allow the continuation of ongoing systemic therapy, also known as treatment beyond progression (TBP). : We retrospectively reviewed 214 selected MM patients who developed oligoprogression during treatment with v-Raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen-activated-extracellular signal-regulated kinase (MEK) or programmed cell death protein 1 (PD-1) inhibitors and received a local treatment continuing TBP.

Exome sequencing in schizophrenic patients with high levels of homozygosity identifies novel and extremely rare mutations in the GABA/glutamatergic pathways.

Inbreeding is a known risk factor for recessive Mendelian diseases and previous studies have suggested that it could also play a role in complex disorders, such as psychiatric diseases. Recent inbreeding results in the presence of long runs of homozygosity (ROHs) along the genome, which are also defined as autozygosity regions. Genetic variants in these regions have two alleles that are identical by descent, thus increasing the odds of bearing rare recessive deleterious mutations due to a homozygous state.

Sorafenib induces variations of the DNA methylome in HA22T/VGH human hepatocellular carcinoma-derived cells.

Sorafenib is currently used to treat advanced and/or unresectable hepatocellular carcinoma (HCC), but the increase of the median survival was only 3 months. Moreover, sorafenib has severe side effects and patients develop resistance quickly. Epigenetic alterations such as DNA methylation play a decisive role in the development and progression of HCC.

SNP array and FISH analysis of a proband with a 22q13.2- 22qter duplication shed light on the molecular origin of the rearrangement.

Background: In about one third of healthy subjects, the microscopic analysis of chromosomes reveals heteromorphisms with no clinical implications: for example changes in size of the short arm of acrocentric chromosomes. In patients with a pathological phenotype, however, a large acrocentric short arm can mask a genomic imbalance and should be investigated in more detail. We report the first case of a chromosome 22 with a large acrocentric short arm masking a partial trisomy of the distal long arm, characterized by SNP array.

Long-term response of gemcitabine plus docetaxel chemotherapy regimen for extraskeletal osteosarcoma: A case report.

Extraskeletal osteosarcomas (EOSs) are rare variants of primary osteosarcoma of the bone, and are defined as sarcomas located in the soft tissues and characterized by osteoid production. EOS exhibits distinctive demographic, imaging and prognostic features compared with osteosarcoma of bone origin. The available data are contradictory with regard to the use of chemotherapy regimens in the management of EOS.

Insights in the etiopathology of galactosyltransferase II (GalT-II) deficiency from transcriptome-wide expression profiling of skin fibroblasts of two sisters with compound heterozygosity for two novel mutations.

Mutations in , encoding the galactosyltransferase II (GalT-II) involved in the synthesis of the glycosaminoglycan (GAG) linkage region of proteoglycans (PGs), have recently been associated with a spectrum of connective tissue disorders, including spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) and Ehlers-Danlos-like syndrome. Here, we report on two sisters compound heterozygous for two novel mutations that presented with severe short stature and progressive kyphoscoliosis, joint hypermobility and laxity, hyperextensible skin, platyspondyly, short ilia, and elbow malalignment. Microarray-based transcriptome analysis revealed the differential expression of several genes encoding extracellular matrix (ECM) structural components, including , , , and , enzymes involved in GAG synthesis and in ECM remodeling, such as , , , and , signaling transduction molecules of the TGFβ/BMP pathway, i.

Copy number variants in attention-deficit hyperactive disorder: identification of the 15q13 deletion and its functional role.

Objectives: Evidence has supported a role for rare copy number variants in the etiology of attention-deficit hyperactivity disorder (ADHD), in particular, the region 15q13, which is also a hot spot for several neuropsychiatric disorders. This region spans several genes, but their role and the biological implications remain unclear.

Methods: We carried out, for the first time, an analysis of the 15q13 region in an Italian cohort of 117 ADHD patients and 77 controls using the MLPA method, confirmed by a genome single-nucleotide polymorphism array.

De novo 1Mb interstitial deletion of 8p22 in a patient with slight mental retardation and speech delay.

We report on a nine years old girl born after 41 weeks of normal gestation with psychomotor retardation, speech delay and minimal dysmorphic signs: antimongolic cut eyes, small mouth, short philtrum and hypertelorism. The use of the high-resolution Affymetrix Human Mapping GeneChip 250 K NspI array allowed the characterization of a de novo 1Mb deletion on the short arm (p22) of a chromosome 8. Molecular cytogenetic-FISH with BAC probes (RP11) confirmed the deletion.

Clinical and molecular characterization of 40 patients with classic Ehlers-Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations.

Background: Classic Ehlers-Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect.

Methods: This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology.

De novo deletion of chromosome 2q24.2 region in a mentally retarded boy with muscular hypotonia.

To date, more than 100 cases with a deletion of chromosome 2q have been identified, although studies reporting small interstitial deletions involving the 2q24.2-q24.3 region are still rare.

New copy number variations in schizophrenia.

Genome-wide screenings for copy number variations (CNVs) in patients with schizophrenia have demonstrated the presence of several CNVs that increase the risk of developing the disease and a growing number of large rare CNVs; the contribution of these rare CNVs to schizophrenia remains unknown. Using Affymetrix 6.0 arrays, we undertook a systematic search for CNVs in 172 patients with schizophrenia and 160 healthy controls, all of Italian origin, with the aim of confirming previously identified loci and identifying novel schizophrenia susceptibility genes.

Evidences for insulator activity of the 5'UTR of the Drosophila melanogaster LTR-retrotransposon ZAM.

Insulators or chromatin boundary are DNA elements that organize the genome into discrete regulatory domains by limiting the actions of enhancers and silencers through a "positional-blocking mechanism". The role of these sequences, both in modulation of the enhancers range of action (enhancer-promoter selectivity) and in the organization of the chromatin in functional domains, is emerging strongly in these last years. There is a great interest in identifying new insulators because deeper knowledge of these elements can help understand how cis-regulatory elements coordinate the expression of the target genes.