Details

Autor(en) / Beteiligte

• Jimenez-Sainz, J.
• Jensen, R.B.

Titel

Abstract GMM-033: CONDITIONAL BRCA2 SWITCH IN HUMAN CELLS TO STUDY TUMOR PROGRESSION

Ist Teil von

• Clinical cancer research, 2019-11, Vol.25 (22_Supplement), p.GMM-033-GMM-033

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Abstract The BRCA2 (Breast Cancer Susceptibility 2) gene is a caretaker of genome integrity. Germline mutations in BRCA2 predispose individuals to a high risk for ovarian and breast cancer. The BRCA2 protein plays an important role in repair of DNA double-strand breaks (DSBs) by homologous recombination. The hallmarks found in BRCA2 mutant tumors involve: genome instability including chromosome aberrations, sensitivity to cross-linking agents, presence of micronuclei, an abnormal number of centrosomes, and severe defects in homologous recombination. However, the initial steps of tumor progression in BRCA2 carriers remain elusive as the majority of cellular models are derived from tumor cell lines that have undergone prior selection in an environment of genomic instability. Here, we present the generation of isogenic, inducible BRCA2 human fallopian tube cell lines providing a model to study the acute loss of BRCA2 protein in the setting of initiation and progression towards tumorigenesis. In these otherwise normal human somatic cells, we have found that acute loss of BRCA2 impinges upon viability as well as other cellular abnormalities that may drive the accumulation and tolerance for further somatic mutations. We have discovered copy number variations modulated by crosslinking compounds in our inducible BRCA2 human fallopian tube cells. We are analyzing both the genetic and biochemical functions of BRCA2 in these processes. Our long-term goal is to elucidate the underlying molecular mechanisms that drive and sustain tumor initiation in the absence of normal BRCA2 function. Citation Format: Jimenez-Sainz J., and Jensen R.B.. CONDITIONAL BRCA2 SWITCH IN HUMAN CELLS TO STUDY TUMOR PROGRESSION [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-033.