Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients.

BACKGROUND: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. RESULTS: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. CONCLUSION: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.

Tendencia en el reporte de casos de cáncer en Oncólogos del Occidente, Pereira, Colombia / Trends in the record of cancer cases at Oncólogos del Occidente, Pereira, Colombia

Introducción: Se describe una serie casos de cáncer en el periodo 2001-2011 de usuarios atendidos en Oncólogos del Occidente que permite establecer una tendencia de la notificación de los casos a través del tiempo. Métodos: Se diseñó un sistema de información de cáncer en Oncólogos del Occidente tomando como fuente la historia clínica digital de la institución. Resultados: En el periodo de observación, los cánceres que más generan consulta en las diferentes sedes de Oncólogos del Occidente están localizados en próstata, mama, cérvix, gástrico, bronquios y pulmón, linfomas, colon, recto, tiroides, ovario y leucemias linfoides. Discusión: Casi todos los cánceres aquí definidos como importantes por su frecuencia pueden ser intervenidos de una manera precoz, con adecuados programas de promoción de la salud y tamizajes que son costo-efectivos.

Introduction: The document establishes the tendencies of cancer cases through time. It describes the series of cancer cases for patients who attended the Oncologos del Occidente during the period of 2001-2011. Methods: To accomplish this, Oncologos del Occidente designed an information system that used as a main source the digital clinical history of the institution. Results: During the period of observation, the most prevalent cancers requiring medical consultation throughout the centers of Oncologos del Occidente were: prostate, breast, cervical, stomach, bronchial tubes and lung, lymphoma, colon, rectum, thyroid, ovarian, and lymphoid leukemia. Discussion: Most of the cancers defined as important by their frequency in this document, can be early intervened through appropriate cost-effective health and screening promotional programs.