An investigation of plasma cell-free RNA for the detection of colorectal cancer: From transcriptome marker selection to targeted validation.

Regular screening for colorectal cancer (CRC) is critical for early detection and long-term survival. Despite the current screening options available and advancements in therapies there will be around 53,000 CRC related deaths this year. There is great interest in non-invasive alternatives such as plasma cell-free RNA (cfRNA) for diagnostic, prognostic, and predictive applications.

Genomic landscape of diploid and aneuploid microsatellite stable early onset colorectal cancer.

Although colorectal cancer (CRC) remains the second leading cause of cancer-related death in the United States, the overall incidence and mortality from the disease have declined in recent decades. In contrast, there has been a steady increase in the incidence of CRC in individuals under 50 years of age. Hereditary syndromes contribute disproportionately to early onset CRC (EOCRC).

Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma.

Purpose: To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation.

Patients And Methods: Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53.

Tracing the potential of networks to improve community cancer care: an in-depth single case study.

Background: Despite overall declines in cancer mortality in the USA over the past three decades, many patients in community settings fail to receive evidence-based cancer care. Networks that link academic medical centers (AMCs) and community providers may reduce disparities by creating access to specialized expertise and care, but research on network effectiveness is mixed. The objective of this study was to identify factors related to whether and how an exemplar AMC network served to provide advice and referral access in community settings.

Novel methylated DNA markers accurately discriminate Lynch syndrome associated colorectal neoplasia.

Acquired molecular changes in Lynch syndrome (LS) colorectal tumors have been largely unstudied. We identified methylated DNA markers (MDMs) for discrimination of colorectal neoplasia in LS and determined if these MDMs were comparably discriminant in sporadic patients. For LS discovery, we evaluated DNA from 53 colorectal case and control tissues using next generation sequencing.

Shorter Treatment-Naïve Leukocyte Telomere Length is Associated with Poorer Overall Survival of Patients with Pancreatic Ductal Adenocarcinoma.

Background: Critically shortened telomeres contribute to chromosomal instability and neoplastic transformation and are associated with early death of patients with certain cancer types. Shorter leukocyte telomere length (LTL) has been associated with higher risk for pancreatic ductal adenocarcinoma (PDAC) and might be associated also with survival of patients with PDAC. We investigated the association between treatment-naïve LTL and overall survival of patients with incident PDAC.

ARC Is a Critical Protector against Inflammatory Bowel Disease (IBD) and IBD-Associated Colorectal Tumorigenesis.

The key functional molecules involved in inflammatory bowel disease (IBD) and IBD-induced colorectal tumorigenesis remain unclear. In this study, we found that the apoptosis repressor with caspase recruitment domain (ARC) protein plays critical roles in IBD. ARC-deficient mice exhibited substantially higher susceptibility to dextran sulfate sodium (DSS)-induced IBD compared with wild-type mice.

AGA Clinical Practice Update on Young Adult-Onset Colorectal Cancer Diagnosis and Management: Expert Review.

Description: The objectives of this expert review are: (1) to prepare clinicians to recognize the presentation and evidence-based risk factors for young adult-onset colorectal cancer (CRC), defined as CRC diagnosed in individuals 18 - <50 years of age; (2) to improve management for patients with young onset CRC. This review will focus on the following topics relevant to young adult-onset CRC: epidemiology and risk factors; clinical presentation; diagnostic and therapeutic management including options for colorectal and extra-colonic surgical intervention, chemotherapy and immune-oncology therapies; genetic testing and its potential impact on preimplantation genetics; fertility preservation; and cancer surveillance recommendations for these individuals and their family members.

Methods: The evidence reviewed in this manuscript is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines.

Leukocyte Telomere Length and Its Interaction with Germline Variation in Telomere-Related Genes in Relation to Pancreatic Adenocarcinoma Risk.

Background: Leukocyte telomere length (LTL) has been associated with risk of multiple cancers, but its association with pancreatic ductal adenocarcinoma (PDAC) is unclear. We therefore investigated the association between peripheral blood LTL and PDAC risk, and examined effect modification by candidate SNPs previously reported to be associated with variation in LTL.

Methods: A case-control study of 1,460 PDAC cases and 1,459 frequency-matched controls was performed using biospecimens and data from the Mayo Clinic Biospecimen Resource for Pancreas Research.

Telomere Length and Risk of Major Adverse Cardiac Events and Cancer in Obstructive Sleep Apnea Patients.

Telomere length (TL) is associated with cardiovascular disease (CVD) and cancer. Obstructive sleep apnea (OSA) is also linked to higher risk of CVD and cancer, and to TL. We investigated the association between TL and risk of major adverse cardiac events (MACE) and cancer in OSA patients.

MetaMarker: a pipeline for de novo discovery of novel metagenomic biomarkers.

Summary: We present MetaMarker, a pipeline for discovering metagenomic biomarkers from whole-metagenome sequencing samples. Different from existing methods, MetaMarker is based on a de novo approach that does not require mapping raw reads to a reference database. We applied MetaMarker on whole-metagenome sequencing of colorectal cancer (CRC) stool samples from France to discover CRC specific metagenomic biomarkers.

EUS fine-needle pancreatic core biopsy can determine eligibility for tumor-agnostic immunotherapy.

The US FDA recently approved a cancer treatment with pembrolizumab based upon the tumor biomarker status of deficient mismatch repair (dMMR) rather than a specific disease-based approach. We sought to determine if endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) could determine dMMR and quantification of PD-L1 expression to potentially guide the delivery of tumor agnostic immunotherapy.  Immunohistochemistry was performed on archived pancreas core biopsy specimens.

Association of telomere length with general cognitive trajectories: a meta-analysis of four prospective cohort studies.

To investigate the association of telomere length (TL) with trajectories of general cognitive abilities, we used data on 5955 participants from the Sex Differences in Health and Aging Study and the Swedish Adoption/Twin Study of Aging in Sweden, and the Mayo Clinic Study of Aging, and the Health and Retirement Study in the United States. TL was measured at baseline, while general cognitive ability was assessed repeatedly up to 7 occasions. Latent growth curve models were used to examine the associations.

Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma.

Gastric adenocarcinoma is the third most common cause of cancer mortality worldwide. Accurate and affordable noninvasive detection methods have potential value for screening and surveillance. Herein, we identify novel methylated DNA markers (MDM) for gastric adenocarcinoma, validate their discrimination for gastric adenocarcinoma in tissues from geographically separate cohorts, explore marker acquisition through the oncogenic cascade, and describe distributions of candidate MDMs in plasma from gastric adenocarcinoma cases and normal controls.

Loss of ZG16 is associated with molecular and clinicopathological phenotypes of colorectal cancer.

Background: Zymogen granule protein 16 (ZG16) is one of the most significantly down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to further evaluate its expression changes and investigate its association with molecular and clinicopathological characteristics of CRC.

Methods: We applied quantitative RT-PCR to determine expression difference between tumor and matched normal tissues from 23 CRC patients.

Colonoscopy surveillance for high risk polyps does not always prevent colorectal cancer.

Aim: To determine the frequency and risk factors for colorectal cancer (CRC) development among individuals with resected advanced adenoma (AA)/traditional serrated adenoma (TSA)/advanced sessile serrated adenoma (ASSA).

Methods: Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study.

Inferring modes of evolution from colorectal cancer with residual polyp of origin.

Besides the classical evolutionary model of colorectal cancer (CRC) defined by the stepwise accumulation of mutations in which normal epithelium transforms through an intermediary polyp stage to cancer, a few studies have proposed alternative modes of evolution (MOE): early eruptive subclonal expansion, branching of the subclones in parallel evolution, and neutral evolution. However, frequencies of MOEs and their connection to mutational characteristics of cancer remain elusive. In this study, we analyzed patterns of somatic single nucleotide variations (SNVs) and copy number aberrations (CNAs) in CRC with residual polyp of origin from 13 patients in order to determine this relationship.

Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations.

The majority of colorectal cancer (CRC) arises from precursor lesions known as polyps. The molecular determinants that distinguish benign from malignant polyps remain unclear. To molecularly characterize polyps, we utilized Cancer Adjacent Polyp (CAP) and Cancer Free Polyp (CFP) patients.

A mutational comparison of adult and adolescent and young adult (AYA) colon cancer.

Background: It is possible that the relative lack of progress in treatment outcomes among adolescent and young adult (AYA) patients with cancer is caused by a difference in disease biology compared with the corresponding diseases in younger and older individuals. There is evidence that colon cancer is more aggressive and has a poorer prognosis in AYA patients than in older adult patients.

Methods: To further understand the molecular basis for this difference, whole-exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2 pediatric colon cancers.

Draft Genome Sequence of Isolate WWM1085, Obtained from a Human Stool Sample.

is a common inhabitant of the human gut. Here, we present a draft genome sequence of isolate WWM1085, obtained from a human stool sample. This sequence will improve our understanding of the genetic diversity of this human-associated methanogen.

Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening.

Obstructive sleep apnea (OSA) is associated with cardiometabolic diseases. Telomere shortening is linked to hypertension, diabetes mellitus, and cardiovascular diseases. Because these conditions are highly prevalent in OSA, we hypothesized that telomere length (TL) would be reduced in OSA patients.

Novel Approach to Fecal Occult Blood Testing by Assay of Erythrocyte-Specific microRNA Markers.

Background: Fecal occult blood testing (FOBT) has historically relied on methods to detect hemoglobin with no fundamental innovations in decades.

Aim: To examine microRNA (miRNA) as a new marker class for FOBT.

Methods: Candidate miRNA markers were identified by small RNA sequencing of human whole blood compared to colorectal epithelia.

Individualized Medicine in Gastroenterology and Hepatology.

After the completion of the Human Genome Project, there has been an acceleration in methodologies on sequencing nucleic acids (DNA and RNA) at a high precision and with ever-decreasing turnaround time and cost. Collectively, these approaches are termed next-generation sequencing and are already affecting the transformation of medical practice. In this symposium article, we highlight the current knowledge of the genetics of selected gastrointestinal tract and liver diseases, namely, inflammatory bowel disease, hereditary cholestatic liver disease, and familial colon cancer syndromes.