Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study.

Familial predisposition is a strong risk factor for different types of cancer and accounts for around 10% of the cases. In this study, we investigated cancer predisposition in a Palestinian family using whole-exome sequencing (WES) technologies. In this study, we focused more on cutaneous melanoma (CM). Our analysis identified three heterozygous rare missense variants, WRN (p.L383F and p.A995T) and TYRP1 (p.T262M) and a pathogenic homozygous missense mutation in ERCC2 (p.R683Q). Although WRN and TYRP1 genes and their variations were correlated with different types of cancer, including melanoma, the currently identified WRN and TYRP1 variants were not reported previously in melanoma cases. The pathogenic mutation was segregated with the clinical phenotypes and found in the two affected brothers, one with CM and the other with brain tumor, and was confirmed by Sanger sequencing analysis. Segregation analysis of this mutation revealed that family members are either heterozygous or wild type. Our findings confirm that the homozygous ERCC2 (p.R683Q) mutation was responsible for causing melanoma and other cancer types in the family. Our work highlights the value to decipher the mutational background of familial cancers, especially CM, in the Palestinian population to guide diagnosis, prevention, and treatment of affected patients and their families.

The future of affordable cancer immunotherapy.

The treatment of cancer was revolutionized within the last two decades by utilizing the mechanism of the immune system against malignant tissue in so-called cancer immunotherapy. Two main developments boosted cancer immunotherapy: 1) the use of checkpoint inhibitors, which are characterized by a relatively high response rate mainly in solid tumors; however, at the cost of serious side effects, and 2) the use of chimeric antigen receptor (CAR)-T cells, which were shown to be very efficient in the treatment of hematologic malignancies, but failed to show high clinical effectiveness in solid tumors until now. In addition, active immunization against individual tumors is emerging, and the first products have reached clinical approval. These new treatment options are very cost-intensive and are not financially compensated by health insurance in many countries. Hence, strategies must be developed to make cancer immunotherapy affordable and to improve the cost-benefit ratio. In this review, we discuss the following strategies: 1) to leverage the antigenicity of "cold tumors" with affordable reagents, 2) to use microbiome-based products as markers or therapeutics, 3) to apply measures that make adoptive cell therapy (ACT) cheaper, e.g., the use of off-the-shelf products, 4) to use immunotherapies that offer cheaper platforms, such as RNA- or peptide-based vaccines and vaccines that use shared or common antigens instead of highly personal antigens, 5) to use a small set of predictive biomarkers instead of the "sequence everything" approach, and 6) to explore affordable immunohistochemistry markers that may direct individual therapies.

Identification of founder and novel mutations that cause congenital insensitivity to pain (CIP) in palestinian patients.

BACKGROUND: Congenital insensitivity to pain (CIP) is a rare autosomal recessive disorder characterized primarily by an inability to perceive physical pain from birth, resulting in the accumulation of bruising, inflammation, and fractures that affect patient's life expectancy. CIP has different forms including CIP and CIPA. CIP with Anhidrosis (CIPA) is the most common type of CIP, which is caused mainly by mutations in NTRK1 and NGF genes, and is characterized by mental retardation and the inability to sweat (Anhidrosis). Because of high consanguinity rates in Palestine, this rare disease appears to have a higher frequency than in other communities. However, there were no systematic studies to address the genetic factors that cause CIP in the Palestinian community. METHODS: In our study, we used Sanger and Whole exome sequencing to genotype members of five CIP-affected Palestinian families. RESULTS: Our results confirm the presence of the founder c.1860-1861insT mutation in the NTRK1 gene of Palestinian Bedouin CIPA patients. Furthermore, one CIPA family carried a missense c.2170 G > A (G724 S) mutation in exon 16 of the NTRK1 gene. Finally, a novel nonsense c.901 A > T mutation (K301*) was detected in exon 7 of the SCN9A gene in CIP without anhidrosis family. CONCLUSIONS: Our study revealed three mutations that cause CIP and CIPA in the Palestinian community, which can help in improving the process of diagnosis and genetic counseling and establishing protocols for the diagnosis and follow-up for the affected individuals. This is especially important given that early diagnosis and medical care interference can prevent unpleasant CIP and CIPA complications.

Genomic epidemiology of the first epidemic wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Palestine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the COVID-19 pandemic, continues to cause a significant public-health burden and disruption globally. Genomic epidemiology approaches point to most countries in the world having experienced many independent introductions of SARS-CoV-2 during the early stages of the pandemic. However, this situation may change with local lockdown policies and restrictions on travel, leading to the emergence of more geographically structured viral populations and lineages transmitting locally. Here, we report the first SARS-CoV-2 genomes from Palestine sampled from early March 2020, when the first cases were observed, through to August of 2020. SARS-CoV-2 genomes from Palestine fall across the diversity of the global phylogeny, consistent with at least nine independent introductions into the region. We identify one locally predominant lineage in circulation represented by 50 Palestinian SARS-CoV-2, grouping with genomes generated from Israel and the UK. We estimate the age of introduction of this lineage to 05/02/2020 (16/01/2020-19/02/2020), suggesting SARS-CoV-2 was already in circulation in Palestine predating its first detection in Bethlehem in early March. Our work highlights the value of ongoing genomic surveillance and monitoring to reconstruct the epidemiology of COVID-19 at both local and global scales.

Seroprevalence of SARS-CoV-2 in the West Bank region of Palestine: a cross-sectional seroepidemiological study.

OBJECTIVES: Seroprevalence rates are important indicators to the epidemiology of COVID-19 and the extent of the pandemic given the existence of asymptomatic cases. The purpose of this study is to assess the seroprevalence rate in the Palestinian population residing in the West Bank. SETTING: The study involved 1355 participants from 11 governorates, including 112 localities in the West Bank and 1136 individuals visiting Palestinian medical laboratories. PARTICIPANTS: Blood samples were collected between 15th June 2020 and 30th June 2020 from 1355 individuals from randomly selected households in the West Bank, in addition to 1136 individuals visiting Palestinian medical laboratories between the 1st May 2020 and 9th July 2020 for a routine check-up. PRIMARY AND SECONDARY OUTCOME MEASURES: Out of the 2491 blood samples collected, serological tests for 2455 adequate serum samples were done using an immunoassay for qualitative detection of antibodies against SARS-CoV-2. Seroprevalence was estimated as the proportion of individuals who had a positive result in the total SARS-CoV-2 antibodies in the immunoassay. RESULTS: The random sample of Palestinians living in the West Bank yielded 0% seroprevalence with 95% and an adjusted CI (0% to 0.0043%), while the lab referral samples yielded an estimated seroprevalence of 0.354% with 95% and an adjusted CI (0.001325% to 0.011566%). CONCLUSIONS: Our results indicate that as of mid-June 2020, seroprevalence in Palestine persists low and is inadequate to provide herd immunity, emphasising the need to maintain health measures to keep the outbreak under control. Population-based seroprevalence studies are to be conducted periodically to monitor the SARS-CoV-2 seroprevalence in Palestine and inform policymakers about the efficacy of their surveillance system.

Altered Expression Pattern of CD55 and CD59 on Red Blood Cells in Anemia of Chronic Kidney Disease.

OBJECTIVE: The aim of this study was to investigate the expression pattern of CD55 and CD59 on red blood cells (RBCs) in anemic chronic kidney disease (CKD) patients, and factors that might influence their expression. SUBJECTS AND METHODS: Nighty-one adult anemic CKD patients and 80 healthy controls (HCs) were enrolled. Anemic CKD patients were divided into 3 subgroups based on receiving erythropoietin and renal replacement therapies. Flow cytometric analysis of CD55 and CD59 expression was performed on RBCs from blood samples obtained from CKD patients and HCs. RESULTS: CD59 deficiency was significantly higher among CKD patients than HCs (n = 68, 74.7%, vs. n = 13, 16.3%, respectively; p < 0.001). The median proportions of CD55- and CD59-deficient RBCs in CKD patients were significantly higher compared to HCs (0.34 vs. 0.15, and 4.3 vs. 2.0, p < 0.001 and p < 0.001, respectively). The mean fluorescence intensity (MFI) of CD55 and CD59 expression was significantly lower in CKD patients compared to HCs (1.2 vs. 2.8, and 17.0 vs. 20.3, p < 0.04 and p < 0. 001, respectively). The hemoglobin level was inversely correlated with the proportions of CD55- and CD59-deficient RBCs (r = -0.37, p < 0.001, and r = -0.22, p < 0.02, respectively). The number of CD59-deficient patients was significantly different between the 3 subgroups of CKD patients (p = 0.001), and a significant difference was present in the MFI of CD55 and CD59 expression among the 3 subgroups (p = 0.04 and p = 0.03, respectively). CONCLUSION: The expression pattern of CD55 and CD59 on RBCs is altered in anemic CKD patients, which could play a role in the pathogenesis of anemia in CKD.