Digenic Inheritance of Mutations in Homologous Recombination Genes in Cancer Patients.

Background/objectives: , , , and are known cancer predisposition genes (CPGs), but tumor risk in patients with simultaneous pathogenic variants (PVs) in CPGs remains largely unknown. In this study, we describe six patients from five families with multiple cancers who coinherited a combination of PVs in these genes.

Methods: PVs were identified using NGS DNA sequencing and were confirmed by Sanger.

Deeper insights into long-term survival heterogeneity of pancreatic ductal adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses.

Pancreatic ductal adenocarcinoma (PDAC) is categorized as the leading cause of cancer mortality worldwide. However, its predictive markers for long-term survival are not well known. It is interesting to delineate individual-specific perturbed genes when comparing long-term (LT) and short-term (ST) PDAC survivors and integrate individual- and group-based transcriptome profiling.

Case Report Series: Aggressive HR Deficient Colorectal Cancers Related to BRCA1 Pathogenic Germline Variants.

Objective: The link between and homologous recombination deficiency (HRD) in cancer has gained importance with the emergence of new targeted cancer treatments, while the available data on the role of the gene in colorectal cancer (CRC) remain contradictory. The aim of this case series was to elucidate the role of known pathogenic variants in the development of early-onset CRC.

Design: Patients were evaluated using targeted next generation sequencing, exome sequencing and chromosomal microarray analysis of the paired germline and tumor samples.

Novel Loss of Function Variant in BCKDK Causes a Treatable Developmental and Epileptic Encephalopathy.

Branched-chain amino acids (BCAA) are essential amino acids playing crucial roles in protein synthesis and brain neurotransmission. Branched-chain ketoacid dehydrogenase (BCKDH), the flux-generating step of BCAA catabolism, is tightly regulated by reversible phosphorylation of its E1α-subunit. BCKDK is the kinase responsible for the phosphorylation-mediated inactivation of BCKDH.

Immunity and Breast Cancer: Focus on Eosinophils.

The role of eosinophils, a cell type involved in the immune response to parasitic infections and allergies, has been investigated in different cancer types, in both tumor tissue and at the circulating level. Most studies showed a role mainly in conjunction with immunotherapy in melanomas and lung tumors, while few data are available in breast cancer. In this review, we summarize literature data on breast cancer, showing a prognostic role of circulating eosinophil counts as well as of the presence of tumor tissue infiltration by eosinophils.

Differences in plasma microRNA content impair microRNA-based signature for breast cancer diagnosis in cohorts recruited from heterogeneous environmental sites.

Circulating microRNAs are non-invasive biomarkers that can be used for breast cancer diagnosis. However, differences in cancer tissue microRNA expression are observed in populations with different genetic/environmental backgrounds. This work aims at checking if a previously identified diagnostic circulating microRNA signature is efficient in other genetic and environmental contexts, and if a universal circulating signature might be possible.

Screening of germline mutations in young Rwandan patients with breast cancers.

Background: In Sub-Saharan Africa breast cancer is commonly detected at younger age and the profile is more aggressive with a high mortality rate compared to the European countries. It is suggested that African-specific genetic background plays a key role in this matter. The present study aimed at understanding the role of genetic factors in breast cancer development in young Rwandan.

Blood eosinophilic relative count is prognostic for breast cancer and associated with the presence of tumor at diagnosis and at time of relapse.

Background: Cancer outcome is associated with circulating immune cells, including eosinophils. Here we analyze the relative eosinophil count (REC) in different breast cancer subtypes.

Methods: Stage I-III breast cancer patients were included in the study and classified as REC-high vs low (cutoff 1.

Prevalence of Histological Characteristics of Breast Cancer in Rwanda in Relation to Age and Tumor Stages.

Breast cancer is a complex disease, and it is the most common cause of morbidity and mortality among women worldwide. In Sub-Saharan Africa, the clinical characteristics and tumor profiles of breast cancer are still unknown. In the present study we aimed to determine breast tumor profiles of the Rwandan patients in relation to age and tumor stages.

GREB1L variants in familial and sporadic hereditary urogenital adysplasia and Mayer-Rokitansky-Kuster-Hauser syndrome.

Congenital uterine anomalies (CUA) may have major impacts on the health and social well-being of affected individuals. Their expressivity is variable, with the most severe end of the spectrum being the absence of any fully or unilaterally developed uterus (aplastic uterus), which is a major feature in Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). So far, etiologies of CUA remain largely unknown.

Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy.

Background: Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is expressed in many cancer types, including breast cancer. Here, we analyze kynurenine and tryptophan and their ratio in breast cancer patients and healthy controls.

Predictive and prognostic role of peripheral blood eosinophil count in triple-negative and hormone receptor-negative/HER2-positive breast cancer patients undergoing neoadjuvant treatment.

In current clinical practices, up to 27% of all breast cancer patients receive neoadjuvant chemotherapy. High pathological complete response rate is frequently associated with tumor-infiltrating lymphocytes. Additionally, circulating immune cells are also often linked to chemotherapy response.

Innovative methodology for the identification of soluble biomarkers in fresh tissues.

The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is required for biomarker discovery but is often not available when it is totally required for clinical pathology investigation. Hence, all OMICs studies are done on residual and less clinically relevant biological samples.

Variations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients.

Background: Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure (CHF).

Methods: In this study, we evaluated innovative circulating cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer patients.

Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation.

Transcriptome-wide analysis of natural antisense transcripts shows their potential role in breast cancer.

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense transcripts (ncNAT) are RNA sequences that are complementary and overlapping to those of either protein-coding (PCT) or non-coding transcripts.

Exome copy number variation detection: Use of a pool of unrelated healthy tissue as reference sample.

An increasing number of bioinformatic tools designed to detect CNVs (copy number variants) in tumor samples based on paired exome data where a matched healthy tissue constitutes the reference have been published in the recent years. The idea of using a pool of unrelated healthy DNA as reference has previously been formulated but not thoroughly validated. As of today, the gold standard for CNV calling is still aCGH but there is an increasing interest in detecting CNVs by exome sequencing.

MicroRNAs and Inflammation in Colorectal Cancer.

Colorectal cancers (CRC) are known to be related to inflammatory conditions, and inflammatory bowel diseases increase the relative risk for developing CRC. The use of anti-inflammatory drugs prevents the development of colorectal cancer.Several molecular mediators are connecting the pathways that are involved in inflammatory conditions and in carcinogenesis.

Circulating microRNA-based screening tool for breast cancer.

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative screening procedure to mammography for breast cancer diagnosis.A plasma miRNA profile was determined by RT-qPCR in a cohort of 378 women.

Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers.

Background: The BRCA1 gene plays a key role in triple negative breast cancers (TNBCs), in which its expression can be lost by multiple mechanisms: germinal mutation followed by deletion of the second allele; negative regulation by promoter methylation; or miRNA-mediated silencing. This study aimed to establish a correlation among the BRCA1-related molecular parameters, tumor characteristics and clinical follow-up of patients to find new prognostic factors.

Methods: BRCA1 protein and mRNA expression was quantified in situ in the TNBCs of 69 patients.

Mutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy.

Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive leukoencephalopathy. Homozygosity mapping, whole exome sequencing, and functional studies were used to define the underlying molecular defect.

BRCA1 germline mutation and glioblastoma development: report of cases.

Background: Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma malignancy has ever been highlighted. Here we report two cases of BRCA1 mutated patients who developed a glioblastoma multiform (GBM).

Endothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer.

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression.