Global Phosphoproteomics of BRCA1-deficient mammary tumors in genetic mouse models

ABSTRACT: The aim of the study is to identify differences in the global phosphoproteome across a BRCA1-deficient mouse mammary tumor panel. We have matched PARPi-naive and PARPi-resistant tumors, in which resistance was induced in vivo (mice bearing tumors were treated with PARPi untill the tumors stopped responding). Each pair of matched naive/resistant tumors originate from a different original tumor donor (one can consider each individual donor as an individual patient). From another analysis (RAD51 IRIF) we know that the mechanism of PARPi-resistance in a number of the tumors is driven by alterations in DNA damage response. Therefore, we can divide the tumors into four groups: (A) HR proficient, the exact mechanism not known, (B) HR proficient due to the loss of 53bp1 (TP53BP1), (C) HR proficient due to loss of Rev7 (MAD2L2) and (D) HR deficient, mechanism of resistance not known. Additionally, each tumor from our panel was retransplanted and challenged with 15 Gy irradiation to trigger a DNA damage response, therefore for each tumor we have an irradiated (IR) and a non-irradiated (NIR) sample. In this experiment each sample was processed in duplicate. Given all this, group (A) consists of 6 individual donors x 2 (matched naive/resistant) x 2 (NIR/IR) x 2 (duplicate) = 48 samples (samples 1-48); groups (B)-(D): 2 donors (per group) x 2 (naive/resistant) x 2 (NIR/IR) x 2 (duplicate) = 16 samples/group (B: samples 65-80, C: samples 81-96 and D: 49-64, according to the OPL label). In total this gives: 48 + 16 +16 +16 = 96 samples. Part of this analysis is used in the paper that also describes data from PXD031711

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Mammary Epithelial Cell, Epithelial Cell

DISEASE(S): Breast Cancer

SUBMITTER: Sander Piersma  

LAB HEAD: Connie Jimenez

PROVIDER: PXD032007 | Pride | 2022-06-06

REPOSITORIES: Pride