The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma.

Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.

The therapeutically actionable long non-coding RNA '' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma.

Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA () that is upregulated in NRAS/MAPK-dependent melanoma, and that we named .

Molecular Genetic Characteristics of , a Proposed New Ovarian Cancer Predisposing Gene.

was recently identified as a new candidate ovarian cancer (OC)-predisposing gene from the genetic analysis of carriers of c.1813C>T; p.L605F in OC families.

A reversible SRC-relayed COX2 inflammatory program drives resistance to BRAF and EGFR inhibition in BRAF colorectal tumors.

BRAF mutation confers a poor prognosis in metastatic colorectal cancer (CRC) despite combinatorial targeted therapies based on the latest understanding of signaling circuitry. To identify parallel resistance mechanisms induced by BRAF-MEK-EGFR co-targeting, we used a high-throughput kinase activity mapping platform. Here we show that SRC kinases are systematically activated in BRAF CRC following targeted inhibition of BRAF ± EGFR and that coordinated targeting of SRC with BRAF ± EGFR increases treatment efficacy in vitro and in vivo.

The Contribution of Germline Pathogenic Variants in Breast Cancer Genes to Contralateral Breast Cancer Risk in -Negative Women.

Background: Contralateral breast cancer (CBC) is associated with younger age at first diagnosis, family history and pathogenic germline variants (PGVs) in genes such as and However, data regarding genetic factors predisposing to CBC among younger women who are -negative remain limited.

Methods: In this nested case-control study, participants negative for // PGVs were selected from the WECARE Study. The burden of PGVs in established breast cancer risk genes was compared in 357 cases with CBC and 366 matched controls with unilateral breast cancer (UBC).

Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling.

Introduction: SARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants.

Methods: We combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8 T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19.

Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes.

Background: Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotype-phenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing.

A functionally impaired missense variant identified in French Canadian families implicates FANCI as a candidate ovarian cancer-predisposing gene.

Background: Familial ovarian cancer (OC) cases not harbouring pathogenic variants in either of the BRCA1 and BRCA2 OC-predisposing genes, which function in homologous recombination (HR) of DNA, could involve pathogenic variants in other DNA repair pathway genes.

Methods: Whole exome sequencing was used to identify rare variants in HR genes in a BRCA1 and BRCA2 pathogenic variant negative OC family of French Canadian (FC) ancestry, a population exhibiting genetic drift. OC cases and cancer-free individuals from FC and non-FC populations were investigated for carrier frequency of FANCI c.

Investigating the clinical, pathological and molecular profile of oncocytic adrenocortical neoplasms: a case series and literature review.

Background: Malignant oncocytic adrenocortical neoplasms (OANs) are rare tumours with a distinctive biological behaviour compared to conventional adrenocortical carcinoma (ACC). The current prognostic systems overestimate the malignant potential of these tumours, and guidance for surveillance and treatment strategies are lacking.

Aim: To evaluate the utility of clinical, pathological and molecular markers in predicting the biological behaviour and outcomes of malignant OANs.

Germline pathogenic variants in PALB2 and other cancer-predisposing genes in families with hereditary diffuse gastric cancer without CDH1 mutation: a whole-exome sequencing study.

Background: Germline pathogenic variants in the E-cadherin gene (CDH1) are strongly associated with the development of hereditary diffuse gastric cancer. There is a paucity of data to guide risk assessment and management of families with hereditary diffuse gastric cancer that do not carry a CDH1 pathogenic variant, making it difficult to make informed decisions about surveillance and risk-reducing surgery. We aimed to identify new candidate genes associated with predisposition to hereditary diffuse gastric cancer in affected families without pathogenic CDH1 variants.