Loss of Primary Cilia Potentiates Pathway Activation in Rhabdoid Colorectal Carcinoma: A Series of 21 Cases Showing Ciliary Rootlet CoiledCoil () Alterations.

A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the and Ciliary Rootlet Coiled-Coil (). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing.

18F-FDG PET/MRI for Rectal Cancer TNM Restaging After Preoperative Chemoradiotherapy: Initial Experience.

Objective: F-FDG-PET/MRI is a novel hybrid techinque that has been recently introduced in oncological imaging, showing promising results. The aim of this study is to assess the value of whole-body F-FDG-PET/MRI for predicting the pathological stage of locally advanced rectal cancer after preoperative chemoradiotherapy.

Design: This was a prospective observational study.

Tryptophan Metabolism as Source of New Prognostic Biomarkers for FAP Patients.

Familial adenomatous polyposis (FAP), a common inherited form of colorectal cancer (CRC), causes the development of hundreds to thousands of colonic adenomas in the colorectum beginning in early adolescence. In absence of a prophylactic surgery, FAP patients almost inevitably develop CRC by the age of 40 to 50. The lack of valuable prognostic biomarkers for FAP patients makes it difficult to predict when the progression from adenoma to malignant carcinoma occurs.

Toward a better definition of EPCAM deletions in Lynch Syndrome: Report of new variants in Italy and the associated molecular phenotype.

Background: Inherited epimutations of Mismatch Repair (MMR) genes are responsible for Lynch Syndrome (LS) in a small, but well defined, subset of patients. Methylation of the MSH2 promoter consequent to the deletion of the upstream EPCAM gene is found in about 1%-3% of the LS patients and represents a classical secondary, constitutional and tissue-specific epimutation. Several different EPCAM deletions have been reported worldwide, for the most part representing private variants caused by an Alu-mediated recombination.

A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer.

8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome.

Next-generation sequencing for genetic testing of familial colorectal cancer syndromes.

Background: Genetic screening in families with high risk to develop colorectal cancer (CRC) prevents incurable disease and permits personalized therapeutic and follow-up strategies. The advancement of next-generation sequencing (NGS) technologies has revolutionized the throughput of DNA sequencing.

Methods: A series of 16 probands for either familial adenomatous polyposis (FAP; 8 cases) or hereditary nonpolyposis colorectal cancer (HNPCC; 8 cases) were investigated for intragenic mutations in five CRC familial syndromes-associated genes (APC, MUTYH, MLH1, MSH2, MSH6) applying both a custom multigene Ion AmpliSeq NGS panel and conventional Sanger sequencing.

Impact of fecal immunochemical test-based screening programs on proximal and distal colorectal cancer surgery rates: A natural multiple-baseline experiment.

Background: Colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) were found to reduce overall CRC surgery rates, but to the authors' knowledge data by subsite are lacking. The objective of the current study was to assess the impact of FIT-based screening on proximal and distal CRC surgical resection rates.

Methods: The Veneto region in Italy can be subdivided into 3 areas with staggered introduction of FIT-based screening programs: early (2002-2004), intermediate (2005-2007), and late (2008-2009) areas.

High risk of rectal cancer and of metachronous colorectal cancer in probands of families fulfilling the Amsterdam criteria.

Objective: To investigate the risk of metachronous colorectal cancer (CRC), its impact on survival, and the risk of rectal cancer in a cohort of probands meeting the Amsterdam criteria.

Background: Several determinants of decision-making for the management of CRC in patients with a putative diagnosis of Lynch syndrome are scarcely defined, and many of them undergo segmental bowel resection instead of the advised total colectomy.

Methods: A retrospective cohort study was conducted on 65 probands of the Amsterdam-positive families who had surgery for primary CRC and at least 5-year surveillance thereafter.

Factors affecting the treatment of multiple colorectal adenomas.

Background: Currently, no guidelines exist for the treatment of patients with multiple colorectal adenomas (MCRAs) (>10 but <100 synchronous nondiminutive polyps of the large bowel). This retrospective study aimed to investigate the clinical and molecular factors related to different treatments for MCRAs.

Methods: Patients with MCRAs were consecutively enrolled from January 2003 to June 2011.

APC I1307K mutations and forkhead box gene (FOXO1A): another piece of an interesting correlation.

Purpose: Germline nonsense and frameshift mutations in the adenomatous polyposis coli (APC) gene are found in approximately 90% of individuals affected by familial adenomatous polyposis (FAP) and a genotype-phenotype relationship has been observed. Missense mutations have also been found in a few cases, even if their role in FAP is still unknown. An association between a missense mutation, APC I1307K, and the risk of sporadic colorectal cancer (CRC) has been reported.

Integrated analysis of unclassified variants in mismatch repair genes.

Purpose: Lynch syndrome is a genetic disease that predisposes to colorectal tumors, caused by mutation in mismatch repair genes. The use of genetic tests to identify mutation carriers does not always give perfectly clear results, as happens when an unclassified variant is found. This study aimed to define the pathogenic role of 35 variants present in MSH2, MLH1, MSH6, and PMS2 genes identified in our 15-year case study.

The role of MYH gene in genetic predisposition to colorectal cancer: another piece of the puzzle.

Biallelic germline mutations in the MYH gene cause MYH-Associated Polyposis but patients with a single mutation possibly have an increased colorectal cancer (CRC) risk. Using DNA from consecutive CRC patients we carried out a case-control study, with the aim to contribute data on the Italian population. Genotyping of four MYH mutations found two biallelic and two monoallelic carriers among 439 cases, and only one heterozygous individual among 247 age-matched controls.

An investigation on the nature of the peptide at m/z 904, overexpressed in plasma of patients with colorectal cancer and familial adenomatous polyposis.

In an investigation devoted to the search for plasma markers for colorectal cancer (CRC), carried out by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, a series of overexpressed peptides were identified in the plasma of patients. Among them the peptide with molecular weight 903 Da was the most abundant one, with a mean +/- (SD) relative abundance of 37 +/- 17% and a frequency over 60%. Interestingly, also in plasma samples of ten subjects affected by familial adenomatous polyposis (FAP), the peptide with molecular weight 903 was overexpressed.