Candidate genes and quantitative trait loci for grain yield and seed size in durum wheat

Grain yield (YLD) is affected by thousand kernel weight (TKW) which reflects the combination of grain length (GL), grain width (GW) and grain area (AREA). Grain weight is also influenced by heading time (HT) and plant height (PH). To detect candidate genes and quantitative trait loci (QTL) of yield components, a durum wheat recombinant inbred line (RIL) population was evaluated in three field trials. The RIL was genotyped with a 90K single nucleotide polymorphism (SNP) array and a high-density genetic linkage map with 5134 markers was obtained. A total of 30 QTL were detected including 23 QTL grouped in clusters on 1B, 2A, 3A, 4B and 6B chromosomes. A QTL cluster on 2A chromosome included a major QTL for HT co-located with QTL for YLD, TKW, GL, GW and AREA, respectively. The photoperiod sensitivity (Ppd-A1) gene was found in the physical position of this cluster. Serine carboxypeptidase, Big grain 1 and β-fructofuranosidase candidate genes were mapped in clusters containing QTL for seed size. This study showed that yield components and phenological traits had higher inheritances than grain yield, allowing an accurate QTL cluster detection. This was a requisite to physically map QTL on durum genome and to identify candidate genes affecting grain yield

Chasing the Foxo3: Insights into its new mitochondrial lair in colorectal cancer landscape

Colorectal cancer (CRC) poses a formidable challenge in terms of molecular heterogeneity, as it involves a variety of cancer-related pathways and molecular changes unique to an individual’s tumor. On the other hand, recent advances in DNA sequencing technologies provide an unprecedented capacity to comprehensively identify the genetic alterations resulting in tumorigenesis, raising the hope that new therapeutic approaches based on molecularly targeted drugs may prevent the occurrence of chemoresistance. Regulation of the transcription factor FOXO3a in response to extracellular cues plays a fundamental role in cellular homeostasis, being part of the molecular machinery that drives cells towards survival or death. Indeed, FOXO3a is controlled by a range of external stimuli, which not only influence its transcriptional activity, but also affect its subcellular localization. These regulation mechanisms are mediated by cancer-related signaling pathways that eventually drive changes in FOXO3a post-translational modifications (e.g., phosphorylation). Recent results showed that FOXO3a is imported into the mitochondria in tumor cells and tissues subjected to metabolic stress and cancer therapeutics, where it induces expression of the mitochondrial genome to support mitochondrial metabolism and cell survival. The current review discusses the potential clinical relevance of multidrug therapies that drive cancer cell fate by regulating critical pathways converging on FOXO3a

From genetics to histomolecular characterization: An insight into colorectal carcinogenesis in lynch syndrome

Lynch syndrome is a hereditary cancer‐predisposing syndrome caused by germline defects in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. Carriers of pathogenic mutations in these genes have an increased lifetime risk of developing colorectal cancer (CRC) and other malignancies. Despite intensive surveillance, Lynch patients typically develop CRC after 10 years of follow‐up, regardless of the screening interval. Recently, three different molecular models of colorectal carcinogenesis were identified in Lynch patients based on when MMR deficiency is acquired. In the first pathway, adenoma formation occurs in an MMR‐proficient background, and carcinogenesis is characterized by APC and/or KRAS mutation and IGF2, NEU‐ ROG1, CDK2A, and/or CRABP1 hypermethylation. In the second pathway, deficiency in the MMR pathway is an early event arising in macroscopically normal gut surface before adenoma for-mation. In the third pathway, which is associated with mutations in CTNNB1 and/or TP53, the adenoma step is skipped, with fast and invasive tumor growth occurring in an MMR‐deficient context. Here, we describe the association between molecular and histological features in these three routes of colorectal carcinogenesis in Lynch patients. The findings summarized in this review may guide the use of individualized surveillance guidelines based on a patient’s carcinogenesis subtype