An expanded variant list and assembly annotation identifies multiple novel coding and noncoding genes for prostate cancer risk using a normal prostate tissue eQTL data set.

Prostate cancer (PrCa) is highly heritable; 284 variants have been identified to date that are associated with increased prostate cancer risk, yet few genes contributing to its development are known. Expression quantitative trait loci (eQTL) studies link variants with affected genes, helping to determine how these variants might regulate gene expression and may influence prostate cancer risk. In the current study, we performed eQTL analysis on 471 normal prostate epithelium samples and 249 PrCa-risk variants in 196 risk loci, utilizing RNA sequencing transcriptome data based on ENSEMBL gene definition and genome-wide variant data.

Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes.

Background: Mutations in several genes predispose to colorectal cancer. Genetic testing for hereditary colorectal cancer syndromes was previously limited to single gene tests; thus, only a very limited number of genes were tested, and rarely those infrequently mutated in colorectal cancer. Next-generation sequencing technologies have made it possible to sequencing panels of genes known and suspected to influence colorectal cancer susceptibility.

Whole exome sequencing in 75 high-risk families with validation and replication in independent case-control studies identifies TANGO2, OR5H14, and CHAD as new prostate cancer susceptibility genes.

Prostate cancer (PCa) susceptibility is defined by a continuum from rare, high-penetrance to common, low-penetrance alleles. Research to date has concentrated on identification of variants at the ends of that continuum. Taking an alternate approach, we focused on the important but elusive class of low-frequency, moderately penetrant variants by performing disease model-based variant filtering of whole exome sequence data from 75 hereditary PCa families.

Germline miRNA DNA variants and the risk of colorectal cancer by subtype.

MicroRNAs (miRNAs) regulate up to one-third of all protein-coding genes including genes relevant to cancer. Variants within miRNAs have been reported to be associated with prognosis, survival, response to chemotherapy across cancer types, in vitro parameters of cell growth, and altered risks for development of cancer. Five miRNA variants have been reported to be associated with risk for development of colorectal cancer (CRC).

Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort.

Objectives: Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression.

Toward understanding the genetics of regulatory T cells in ovarian cancer.

Tumor-infiltrating regulatory T cells (Tregs) promote immune evasion and are associated with poor disease outcome in patients affected by various malignancies. We have recently demonstrated that several, inherited single nucleotide polymorphisms affecting Treg-related genes influence the survival of ovarian cancer patients, providing novel insights into possible mechanisms of immune escape.

Identification of novel variants in colorectal cancer families by high-throughput exome sequencing.

Background: Colorectal cancer (CRC) in densely affected families without Lynch Syndrome may be due to mutations in undiscovered genetic loci. Familial linkage analyses have yielded disparate results; the use of exome sequencing in coding regions may identify novel segregating variants.

Methods: We completed exome sequencing on 40 affected cases from 16 multicase pedigrees to identify novel loci.

The immune system in the pathogenesis of ovarian cancer.

Clinical outcomes in ovarian cancer are heterogeneous even when considering common features such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling host characteristic is the immune response to ovarian cancer.

Inherited variants in regulatory T cell genes and outcome of ovarian cancer.

Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored.

HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG).

Prostate cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic.

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22.

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e.

Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker.

Early detection of ovarian cancer is difficult owing to the lack of specific and sensitive tests available. Previously, we found expression of nectin 4 to be increased in ovarian cancer compared with normal ovaries. Reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative RT-PCR validated the overexpression of nectin 4 messenger RNA in ovarian cancer compared with normal ovarian cell lines and tissues.

S100A1 expression in ovarian and endometrial endometrioid carcinomas is a prognostic indicator of relapse-free survival.

We sought to investigate the expression levels of S100A1 in ovarian cancer cell lines and tissues to correlate S100A1 with subtype, stage, grade, and relapse-free survival. S100A1 messenger RNA and protein were up-regulated in ovarian cancer cell lines and tumors compared with normal ovarian cell lines and tissues by gene microarray analysis, reverse transcriptase-polymerase chain reaction, quantitative reverse transcriptase-polymerase chain reaction, and Western immunoblotting. In the study, 63.

Early detection of ovarian cancer using group biomarkers.

One reason that ovarian cancer is such a deadly disease is because it is not usually diagnosed until it has reached an advanced stage. In this study, we developed a novel algorithm for group biomarkers identification using gene expression data. Group biomarkers consist of coregulated genes across normal and different stage diseased tissues.