Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients.

Increased genetic risk for melanoma can occur in the context of germline pathogenic variants in high-penetrance genes, such as and , risk variants in low- to moderate-penetrance genes ( and ), and possibly due to variants in emerging genes, such as , and . We aimed to identify germline variants in high- and low- to moderate-penetrance melanoma risk genes in Brazilian patients with clinical criteria for familial melanoma syndrome. We selected patients with three or more melanomas or melanoma patients from families with three tumors (melanoma and pancreatic cancer) in first- or second-degree relatives.

Family-based whole-exome sequencing identifies rare variants potentially related to cutaneous melanoma predisposition in Brazilian melanoma-prone families.

Genetic predisposition accounts for nearly 10% of all melanoma cases and has been associated with a dozen moderate- to high-penetrance genes, including CDKN2A, CDK4, POT1 and BAP1. However, in most melanoma-prone families, the genetic etiology of cancer predisposition remains undetermined. The goal of this study was to identify rare genomic variants associated with cutaneous melanoma susceptibility in melanoma-prone families.

BAP1 tumor predisposition syndrome case report: pathological and clinical aspects of BAP1-inactivated melanocytic tumors (BIMTs), including dermoscopy and confocal microscopy.

Background: BRCA1 associated-protein 1 (BAP1) tumor predisposition syndrome is associated with an increased risk for malignant mesotheliomas, uveal and cutaneous melanomas, renal cell carcinomas, and singular cutaneous lesions. The latter are referred to as BAP1-inactivated melanocytic tumors (BIMTs). When multiple BIMTs manifest, they are considered potential markers of germline BAP1 mutations.

Somatic copy number alterations in pleomorphic adenoma and recurrent pleomorphic adenoma.

Objective: As the genetic changes in recurrent pleomorphic adenoma (RPA) have not yet been investigated, the aim of this study was to assess the genomic profile of somatic copy number alteration in RPA and pleomorphic adenoma (PA) by using array comparative genomic hybridization (aCGH).

Study Design: Four cases of RPA and 13 cases of PA were evaluated by using aCGH, using a 180 K platform. Data were analyzed by using Nexus Copy Number Discovery.

Evaluation of a subset of tumor suppressor gene for copy number and epigenitic changes in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma carcinogenesis.

Objective: The progression of pleomorphic adenoma (PA) to carcinoma ex-pleomorphic adenoma (CXPA) encompasses several genomic alterations involving complex pathways. Tumor suppressor genes seem to play important roles in the tumorigenesis of both tumors. The aim of this study was to evaluate copy number and methylation of tumor suppressor genes' status in PA and CXPA samples.

Role of rare germline copy number variation in melanoma-prone patients.

Aim: This work evaluates a possible causative role for germline copy number variants (CNVs) in melanoma predisposition.

Patients & Methods: A total of 41 melanoma-prone Brazilian patients were investigated for CNVs using 850K single nucleotide polymorphism arrays.

Results: Ten rare CNVs were identified in nine patients, comprising 54 known genes, mostly related to cancer.

Upregulated genes at 2q24 gains as candidate oncogenes in hepatoblastomas.

Aim: Cytogenetic data of hepatoblastomas, a rare embryonal tumor of the liver, mostly consist of descriptions of whole-chromosome aneuploidies and large chromosome alterations. High-resolution cytogenetics may provide clues to hepatoblastoma tumorigenesis and indicate markers with clinical significance.

Patients & Methods: We used array-CGH (180K) to screen for genomic imbalances in nine hepatoblastomas.

Lymphovascular invasion and histologic grade are associated with specific genomic profiles in invasive carcinomas of the breast.

Lymphovascular invasion (LVI) and histologic grade are clinical parameters of high prognostic value in breast cancer and indicate the level of tumor aggressiveness. Many studies have focused on the association of breast cancer subtypes with gene expression and chromosomal profiles, but considerably less genomic information is available regarding traditional prognostic factors such as histologic grade and LVI. We studied by array-CGH a group of 57 invasive ductal carcinomas of the breast to outline the DNA copy number aberration (CNA) profile linked to high histologic grades and LVI.

An inherited small microdeletion at 15q13.3 in a patient with early-onset obsessive-compulsive disorder.

Copy number variations (CNVs) have been previously associated with several different neurodevelopmental psychiatric disorders, such as autism, schizophrenia, and attention deficit hyperactivity disorder (ADHD). The present study consisted of a pilot genome-wide screen for CNVs in a cohort of 16 patients with early-onset obsessive-compulsive disorder (OCD) and 12 mentally healthy individuals, using array-based comparative genomic hybridization (aCGH) on 44K arrays. A small rare paternal inherited microdeletion (∼64 kb) was identified in chromosome 15q13.

Association of melanoma with intraepithelial neoplasia of the pancreas in three patients.

Melanoma and pancreatic cancer are two low frequency types of cancer. In this study, three patients who developed both melanoma and intraepithelial neoplasia of the pancreas were tested for CDKN2A mutations and deletions, and investigated for rare germline copy number variations (CNVs). The three patients were negative for CDKN2A point mutations and intragenic deletions.