The goal of this study was to review relevant case-control trials in order to determine the association of paraoxonase 1 (PON1) gene polymorphisms (-108C/T, 55L/M, 192Q/R) and polycystic ovarian syndrome (PCOS) susceptibility.

Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18-21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGFR mutations highlighting the results of several in vitro and in vivo studies, which singly evaluated the sensitivity of uncommon mutations to currently European of Medicines Agency (EMA)-approved EGFR TKIs in cell lines, xenograft models and humans, in order to obtain a practical guide for refining the clinical decision-making process.

Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that may be a useful prognostic biomarker in nasopharyngeal cancer (NPC). The purpose of this systematic review and meta-analysis was to investigate the relationship between PD-L1 expression and survival in NPC.

To explore clinical, histopathological and immunohistochemistry (IHC) features of mammary analogue secretory carcinoma (MASC) with systematic literature review.

Vasculogenic mimicry (VM) is an intratumoral microcirculation pattern formed by aggressive cancer cells, which mediates tumor growth. In this study, we compiled the evidence from studies evaluating whether positive VM status can serve as a prognostic factor to patients with squamous cell carcinoma of the head and neck (HNSCC) or esophagus (ESCC). Comprehensive systematic searches were conducted using Cochrane Library, Ovid Medline, PubMed, and Scopus databases. We appraised the quality of studies and the potential for bias, and performed random-effect meta-analysis to assess the prognostic impact of VM on the overall survival (OS). Seven studies with 990 patients were eligible, where VM was detected in 34.24% of patients. Positive-VM was strongly associated with poor OS (hazard ratio = 0.50; 95% confidence interval: 0.38-0.64), which remained consistent following the subgroup analysis of the studies. Furthermore, VM was associated with more metastasis to local lymph nodes and more advanced stages of HNSCC and ESCC. In conclusion, this study provides clear evidence showing that VM could serve as a promising prognosticator for patients with either HNSCC or ESCC. Further studies are warranted to assess how VM can be implemented as a reliable staging element in clinical practice and whether it could provide a new target for therapeutic intervention.

Approximately 10-30% of men with mCRPC will test positive for AR-V7 using one of two analytically and clinically validated circulating tumor cell (CTC)-based assays. These men have poor outcomes with approved AR-targeting therapies but may retain sensitivity to chemotherapy. Here, we discuss the clinical implications of testing and strategies that may benefit AR splice variant (AR-V)-positive men and discuss whether such variants are passengers or drivers of aggressive clinical behavior.

ABO gene polymorphisms have been reported to be associated with the risk of multiple cancers and cardiocerebrovascular diseases. However, the results remained controversial. In this study, we conducted a systematic review and meta-analysis to clarify the association between two SNPs (rs505922 and rs657152) in ABO gene and cancers/cardiocerebrovascular diseases.

To make recommendations on the indications for molecular testing regarding the diagnosis, prediction of prognosis, and treatment selection in adult patients with s oft tissue sarcomas (STS) excluding gastrointestinal stromal tumour.

Liquid biopsies (LB) are emerging in the oncology field, with promising data as new diagnostic, prognostic and treatment-monitoring tools. Squamous cell carcinoma of the head and neck (SCCHN) is a heterogenous disease and many challenges remain to improve patient outcomes. Liquid biopsy could be of interest at different stages of SCCHN disease, including better screening to diagnose more patients at an early stage, early detection of relapse after curative treatment, and the implementation of precision medicine. As LB is very attractive by the ease of sampling, this field is moving fast. Therefore, it is important to be aware of the potential applications but also the limitations of these new tools in regards to technical aspects and interpretation of the data. In this review, we will first give an overview of potential clinical applications and technical challenges of circulating tumor DNA (ctDNA) and then focus on current available data of ctDNA in SCCHN. Although the literature on ctDNA analysis for SCCHN is scarce compared to other tumors, preliminary results seem to hold promise for the future, including the detection of minimal residual disease or the detection of potentially targetable events through liquid biopsy. Prospective liquid-biopsy driven clinical trials are needed to validate its clinical relevance.

Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis. As a member of circRNAs, ciRS-7 is thought to be a negative prognostic indicator in multiple types of cancer. The present study aimed to comprehensively explore the value of ciRS-7 in tumor malignancy. Materials and Methods. A systematic review of PubMed, Web of Science, and the Cochrane library was carried out to examine the related studies. The pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from the available publications by STATA 12.0. Subgroup analysis, publication bias, sensitivity analysis, and meta-regression were conducted.

Targeting the programmed death ligand 1 (PD-L1) pathway has become standard for many advanced malignancies. Whether PD-L1 expression predicts response is unclear. We assessed the association between PD-L1 expression and immunotherapy response using stratified meta-analysis.

The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients.

Breast cancer is a molecularly heterogeneous disorder associated with high lethal malignant tumors among women worldwide. Genetic factors play an important role in breast cancer development. Several single nucleotide polymorphisms in the 8q24 region associated with risk of breast cancer have been identified. Fifteen studies including 32,955 cases and 43,716 controls were collected to conduct a meta-analysis to evaluate the associations between variants in 8q24 region and risk of breast cancer. Our study showed that only rs13281615 is associated with breast cancer risk in this large-scale research synopsis and meta-analysis. Further studies are needed to explore the role of the 8q24 variants in the development of breast cancer.

NUT (midline) carcinoma is a rare, highly aggressive, poorly differentiated carcinoma that characteristically harbors a rearrangement of the NUTM1 gene. Most of these tumors occur in adolescents and young adults, arise from the midline structures of the thorax, head, and neck, and are associated with extremely poor outcomes. Rare cases originating from salivary glands have been reported with clinicopathologic features comparable to NUT carcinoma of other sites. Outcome studies regarding this subgroup are currently lacking. We report a case of NUT carcinoma arising in a submandibular gland of a 12-year-old boy. Diagnosis was confirmed by fluorescence in situ hybridization demonstrating fusion of the BRD4 (19p13.12) and NUTM1 (15q14) gene loci. A systematic review of all previously reported salivary gland NUT carcinomas (n = 15) showed exclusive occurrence of pediatric cases (n = 6) in males compared to adult patients (n = 9, male: female = 1:2; p < 0.05). The median survival was 24 and 4 months for pediatric and adult patients, respectively (95% confidence interval was 8-24 and 1-7 months, respectively; p < 0.01). The 1-year overall survival was 67% for pediatric and 11% for adult patients. Among all NUT carcinomas, pediatric salivary gland tumors may represent a distinct clinical subset associated with male predilection and comparatively prolonged survival.

Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is directed by different glycosyltransferases, depending on the cell in which it is expressed. These small carbohydrate molecules consist of multiple glycan families that facilitate cell-cell interactions, protein interactions, and downstream signaling. An alteration of several types of O-glycan core structures have been implicated in multiple cancers, largely due to differential glycosyltransferase expression or activity. Consequently, aberrant O-linked glycosylation has been extensively demonstrated to affect biological function and protein integrity that directly result in cancer growth and progression of several diseases. Herein, we provide a comprehensive review of several initiating enzymes involved in the synthesis of O-linked glycosylation that significantly contribute to a number of different cancers.

New therapeutic approaches in oncology have converted cancer from a certain death sentence to a chronic disease. However, there are still challenges to be overcome regarding the off-target toxicity of many of these treatments. Oncological therapies can lead to future infertility in women. Given this negative impact on long-term quality of life, fertility preservation is highly recommended. While gamete and ovarian tissue cryopreservation are the usual methods offered, new pharmacological-based options aiming to reduce ovarian damage during oncological treatment are very attractive. In this vein, advances in the field of transcriptomics and epigenomics have brought small noncoding RNAs, called microRNAs (miRNAs), into the spotlight in oncology. MicroRNAs also play a key role in follicle development as regulators of follicular growth, atresia and steroidogenesis. They are also involved in DNA damage repair responses and they can themselves be modulated during chemotherapy. For these reasons, miRNAs may be an interesting target to develop new protective therapies during oncological treatment. This review summarizes the physiological role of miRNAs in reproduction. Considering recently developed strategies based on miRNA therapy in oncology, we highlight their potential interest as a target in fertility preservation and propose future strategies to make the transition from bench to clinic.

Introduction: Driver molecular aberrations, such as EGFR and BRAF mutations, ALK and ROS1 rearrangements, play an important role in the oncogenesis of non-small-cell lung cancer (NSCLC). Overall, these molecular targets select about 20% of advanced nonsquamous NSCLC Caucasian patients who can be treated with the corresponding tyrosine kinase inhibitors (TKIs). Many novel driver mutations are being or have been investigated in NSCLC, with varying degrees of success and failure. These emerging molecular targets are responsible for both primary involvement in cancer growth and have acquired resistance to previous TKIs, and for which potential therapeutic strategies are under investigation.Areas covered: This review will focus on the main emerging molecular targets in advanced stage of clinical development for the management of advanced NSCLC. A systematic review of bibliographic databases for peer-reviewed research literature and of key meetings was undertaken in order to discuss these topics.Expert opinion: Many emerging driver mutations are being investigated in metastatic NSCLC. Defining the most appropriate methods of detection of molecular aberrations, focusing on their role in the mechanisms of intrinsic and acquired resistance within appropriate preclinical and clinical trials, are needed in order to improve therapeutic benefit for NSCLC patients.

Endometrial cancer is one of the most commonly diagnosed cancers in women. Although there is a hereditary component to endometrial cancer, most cases are thought to be sporadic and lifestyle related. The aim of this study was to systematically review prospective and retrospective case-control studies, meta-analyses and genome-wide association studies to identify genomic variants that may be associated with endometrial cancer risk.

Fanconi anemia (FA) is a DNA repair disorder resulting from mutations in genes encoding for FA DNA repair complex components and is characterized by variable congenital abnormalities, bone marrow failure (BMF), and high incidences of malignancies. FA mosaicism arises from reversion or other compensatory mutations in hematopoietic cells and may be associated with BMF reversal and decreased blood cell sensitivity to DNA-damaging agents (clastogens); this sensitivity is a phenotypic and diagnostic hallmark of FA. Uncertainty regarding the clinical significance of FA mosaicism persists; in some cases, patients have survived multiple decades without BMF or hematologic malignancy, and in others hematologic failure occurred despite the presence of clastogen-resistant cell populations. Assessment of mosaicism is further complicated because clinical evaluation is frequently based on clastogen resistance in lymphocytes, which may arise from reversion events both in lymphoid-specific lineages and in more pluripotent hematopoietic stem/progenitor cells (HSPCs). In this review, we describe diagnostic methods and outcomes in published mosaicism series, including the substantial intervals (1-6 years) over which blood counts normalized, and the relatively favorable clinical course in cases where clastogen resistance was demonstrated in bone marrow progenitors. We also analyzed published FA mosaic cases with emphasis on long-term clinical outcomes when blood count normalization was identified. Blood count normalization in FA mosaicism likely arises from reversion events in long-term primitive HSPCs and is associated with low incidences of BMF or hematologic malignancy. These observations have ramifications for current investigational therapeutic programs in FA intended to enable gene correction in long-term repopulating HSPCs.

BackgroundRecently, epidemiological studies investigating the association of MTHFR 677 C > T, 1298 A > C and MTR 2756 A > G polymorphism with retinoblastoma susceptibility reported controversial results. Methods: Data were collected from several electronic databases such as PubMed, EMBASE, and Google Scholar databases, with the last search up to December 05, 2019. Results: A total of eleven case-control studies including four studies with 324 cases and 490 controls on MTHFR 677 C > T, four studies with 324 cases and 490 controls on MTHFR 1298 A > C, and three studies with 283 cases and 485 controls on MTR 2756 A > G were selected. There was a significant association between MTHFR 677 C > T and MTR 2756 A > G polymorphisms and an increased risk of retinoblastoma. However, MTHFR 1298 A > C polymorphism was not significantly associated with risk of retinoblastoma. Conclusion: This meta-analysis demonstrated that MTHFR 677 C > T and MTR 2756 A > G polymorphisms might play important roles in the development of retinoblastoma. No association with MTHFR 1298 A > C polymorphism was observed.