Liquid biopsy-based early tumor and minimal residual disease detection.

Genetic predisposition is one of the major measurable cancer risk factors. Affected patients have an enhanced risk for cancer and require life-long surveillance. However, current screening measures are mostly invasive and only available for certain tumor types.

Rearranged ERG confers robustness to prostate cancer cells by subverting the function of p53.

Objective: ERG rearrangements are frequent and early events in prostate cancer. The functional role of rearranged ERG, however, is still incompletely understood. ERG rearrangements are maintained during prostate cancer progression suggesting that they may confer a selective advantage.

High numbers of PDCD1 (PD-1)-positive T cells and mutations in microsatellite-unstable colorectal cancer.

DNA mismatch repair (MMR)-deficient cancers accumulate high numbers of coding microsatellite mutations, which lead to the generation of highly immunogenic frameshift peptide (FSP) neoantigens. MMR-deficient cells can grow out to clinically manifest cancers either if they evade immune cell attack or if local T-cells get exhausted. Therefore, a subset of MSI cancer patients responds particularly well to treatment with immune checkpoint inhibitors.

Successful immune checkpoint blockade in a patient with advanced stage microsatellite-unstable biliary tract cancer.

Cancers acquire multiple somatic mutations that can lead to the generation of immunogenic mutation-induced neoantigens. These neoantigens can be recognized by the host's immune system. However, continuous stimulation of immune cells against tumor antigens can lead to immune cell exhaustion, which allows uncontrolled outgrowth of tumor cells.

Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms.

Background: Mucinous ovarian tumors represent a distinct histotype of epithelial ovarian cancer. The rarest (2-4 % of ovarian carcinomas) of the five major histotypes, their genomic landscape remains poorly described. We undertook hotspot sequencing of 50 genes commonly mutated in human cancer across 69 mucinous ovarian tumors.

Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy.

Analysis of tumor-infiltrating lymphocytes (TIL) in primary human colorectal cancer (CRC) by in situ immunohistochemical staining supports the hypothesis that the adaptive immune response influences the course of human CRC. Specifically, high densities of TILs in the primary tumor are associated with good prognosis independent of other prognostic markers. However, the prognostic role of TILs in metastatic CRC lesions is unknown, as is their role in response or resistance to conventional chemotherapy.

ASTD: The Alternative Splicing and Transcript Diversity database.

The Alternative Splicing and Transcript Diversity database (ASTD) gives access to a vast collection of alternative transcripts that integrate transcription initiation, polyadenylation and splicing variant data. Alternative transcripts are derived from the mapping of transcribed sequences to the complete human, mouse and rat genomes using an extension of the computational pipeline developed for the ASD (Alternative Splicing Database) and ATD (Alternative Transcript Diversity) databases, which are now superseded by ASTD. For the human genome, ASTD identifies splicing variants, transcription initiation variants and polyadenylation variants in 68%, 68% and 62% of the gene set, respectively, consistent with current estimates for transcription variation.

Characterization of humoral immune responses against p16, p53, HPV16 E6 and HPV16 E7 in patients with HPV-associated cancers.

The cellular tumor suppressor p16 is strongly overexpressed in cervical cancers and precancers. We have previously demonstrated that infiltrating T lymphocytes reactive against p16 can be found in cervical cancer patients. Here, we analyzed whether p16 induces humoral immune responses.

The putative tumor suppressor AIM2 is frequently affected by different genetic alterations in microsatellite unstable colon cancers.

Mismatch repair (MMR) deficiency is a major mechanism of colorectal tumorigenesis that is observed in 10-15% of sporadic colorectal cancers and those associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. MMR deficiency leads to the accumulation of mutations mainly at short repetitive sequences termed microsatellites, constituting the high level microsatellite instability (MSI-H) phenotype. In recent years, several genes have been described that harbor microsatellites in their coding region (coding microsatellites, cMS) and are frequently affected by mutations in MMR-deficient cancers.

Absence of association between cyclin D1 (CCND1) G870A polymorphism and age of onset in hereditary nonpolyposis colorectal cancer.

CCND1 encodes cyclin D1, which plays an important role in the G1 to S phase transition of the cell cycle. A common polymorphism (c.G870A) increases alternate splicing.

Relaxation of glycine receptor and onconeural gene transcription control in NRSF deficient small cell lung cancer cell lines.

Negative regulation of many neuronal genes is mediated by the neuron-restrictive silencer factor (NRSF/repressor element-1 binding transcription factor, REST), which binds to the neuron-restrictive silencer element (NRSE/repressor element-1, RE-1) and thereby represses transcription of neuronal genes in non-neuronal cells. Sequence analysis of 5'-flanking regions of glycine receptor (GlyR) subunit genes revealed a consensus motif for NRSE in the GLRA1 and GLRA3, but not in GLRB, genes. In this study, we examined tumor cell lines for the expression of NRSF, GlyR subunits and onconeural genes.

Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin.

The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells.

Pathogenesis of DNA repair-deficient cancers: a statistical meta-analysis of putative Real Common Target genes.

DNA mismatch repair deficiency is observed in about 15% of human colorectal, gastric, and endometrial tumors and in lower frequencies in a minority of other tumors thereby causing insertion/deletion mutations at short repetitive sequences, recognized as microsatellite instability (MSI). Evolution of tumors, including those with MSI, is a continuous process of mutation and selection favoring neoplastic growth. Mutations in microsatellite-bearing genes that promote tumor cell growth in general (Real Common Target genes) are assumed to be the driving force during MSI carcinogenesis.

Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions.

Persistent high risk type human papillomavirus (HR-HPVs) infections induce dysplasia or cancer of the anogenital tract, most notably of the uterine cervix. The viral genome usually persists and replicates as an episomal molecule in early dysplasia, whereas in advanced dysplasia or cervical cancer HPV genomes are frequently integrated into the chromosomal DNA of the host cell. Previous studies suggested that modification of critical cellular sequences by integration of HPV genomes might significantly contribute to the neoplastic transformation of anogenital epithelia (insertional mutagenesis).