Analysis of germline variants in pediatric patients diagnosed with desmoid tumors and nuchal-type fibromas.

Desmoid tumor (DT) is a fibroblastic proliferation arising in soft tissue characterized by localized infiltrative growth with an inability to metastasize but with a tendency to recurrence. Nuchal-type fibromas are benign soft tissue lesions that are usually developed in the posterior neck. The development of these neoplasms can be associated with a hereditary cancer predisposition syndrome, mainly familial adenomatous polyposis (FAP) syndrome caused by germline mutations.

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing.

Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes. The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes.

Splicing-Disrupting Mutations in Inherited Predisposition to Solid Pediatric Cancer.

The prevalence of hereditary cancer in children was estimated to be very low until recent studies suggested that at least 10% of pediatric cancer patients carry a germline mutation in a cancer predisposition gene. A significant proportion of pathogenic variants associated with an increased risk of hereditary cancer are variants affecting splicing. RNA splicing is an essential process involved in different cellular processes such as proliferation, survival, and differentiation, and alterations in this pathway have been implicated in many human cancers.

Identification and Functional Analysis of a Novel Mutation in Pediatric Medulloblastoma.

Medulloblastoma is the primary malignant tumor of the Central Nervous System (CNS) most common in pediatrics. We present here, the histological, molecular, and functional analysis of a cohort of 88 pediatric medulloblastoma tumor samples. The WNT-activated subgroup comprised 10% of our cohort, and all WNT-activated patients had exon 3 mutations and were immunostained for nuclear β-catenin.

Prostate tumor OVerexpressed-1 (PTOV1) down-regulates HES1 and HEY1 notch targets genes and promotes prostate cancer progression.

Background: PTOV1 is an adaptor protein with functions in diverse processes, including gene transcription and protein translation, whose overexpression is associated with a higher proliferation index and tumor grade in prostate cancer (PC) and other neoplasms. Here we report its interaction with the Notch pathway and its involvement in PC progression.

Methods: Stable PTOV1 knockdown or overexpression were performed by lentiviral transduction.

PTOV1 is overexpressed in human high-grade malignant tumors.

The prostate tumor overexpressed-1 (PTOV1) protein was first described overexpressed in prostate cancer but not detected in normal prostate. PTOV1 expression is associated to increased cancer proliferation in vivo and in vitro. In prostate biopsy, PTOV1 detection is helpful in the early diagnosis of cancer.

PTOV1 expression predicts prostate cancer in men with isolated high-grade prostatic intraepithelial neoplasia in needle biopsy.

Purpose: To analyze the expression of PTOV1 in high-grade prostatic intraepithelial neoplasia (HG-PIN) and to explore its usefulness to predict prostate cancer in patients with isolated HG-PIN in needle biopsy (prostate needle biopsy).

Experimental Design: PTOV1 expression in HG-PIN lesions from 140 patients was analyzed by immunohistochemistry in a semiquantitative manner (Histo-score). HG-PIN derived from 79 radical prostatectomies for prostate cancer and from 11 cistoprostatectomies for bladder cancer without prostate cancer were used as positive and negative controls, respectively.

Apoptotic and anti-proliferative effects of all-trans retinoic acid. Adenine nucleotide translocase sensitizes HeLa cells to all-trans retinoic acid.

We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation.