GEO series

Codon Specific Readthrough as a Mechanism of BRCA2 Restoration in Acquired PARP Inhibitor and Chemotherapy Resistance [RNA-seq]

GSE243141 Homo sapiens (human) RNA-seq (gene expression) 10 samples Submitted 2025/10/22 Platform GPL11154

At a glance

RNA-seq (gene expression) · human · 10 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 10 samples: 5 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Deleterious alterations of the gene encoding BRCA2, a protein involved in homologous recombination (HR), contribute to the pathogenesis of a subset of ovarian, breast, prostate and pancreatic cancers as well as their increased sensitivity to platinating agents and poly(ADP-ribose) polymerase inhibitors (PARPis). While secondary mutations that restore a functional BRCA2 protein are detected in a fraction of cases that become drug resistant, the causes of resistance in other cases are poorly understood.

Read the full summary ↓

Here we characterized clones derived from the BRCA2-mutant ovarian cancer line PEO1 by PARPi selection. Colony forming assays demonstrated cross-resistance of these clones to multiple PARPis, cisplatin and doxorubicin. Despite persistence of the signature 4965C>G (p.Y1655X) BRCA2 nonsense mutation, HR was restored in the resistant cells. Immunoprecipitation followed by immunoblotting or mass spectrometry demonstrated expression of low levels of BRCA2 protein, including peptides distal to the premature termination codon. Reporter assays demonstrated readthrough selective for the UAG stop codon in the resistant clones but not parental PEO1 cells. Mass spectrometry and immunoblotting provided evidence for readthrough of stop codons, particularly UAGs, in additional proteins in the resistant clones. BRCA2 gene interruption either 5’ or 3’ to the stop codon restored sensitivity of the resistant clones to PARPis and cisplatin, implicating the low level BRCA2 expression in resistance. Accordingly, the present results identify low level readthrough of nonsense codons as a potential mechanism of drug resistance that might need to be considered when assessing the impact of BRCA2 nonsense mutations.

This dataset

Open GSE243141 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE243141_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1016425 and SRA study SRP460346. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

5 conditions, mostly in duplicate

ABTr1 ×2 ABTr2 ×2 ABTr3 ×2 ABTr4 ×2 PEO1 ×2

Supports a between-group comparison across 10 samples.

How we read this: 5 replicated groups read from 10 sample titles; they account for 10 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM7779863 ABTr1-1 ABTr1
GSM7779864 ABTr1-2 ABTr1
GSM7779865 ABTr2-1 ABTr2
GSM7779866 ABTr2-2 ABTr2
GSM7779867 ABTr3-1 ABTr3
GSM7779868 ABTr3-2 ABTr3
GSM7779869 ABTr4-1 ABTr4
GSM7779870 ABTr4-2 ABTr4
GSM7779871 PEO1-1 PEO1
GSM7779872 PEO1-2 PEO1

Datasets on a similar topic

GSE243143 Codon Specific Readthrough as a Mechanism of BRCA2 Restoration in Acquired PARP Inhibitor and Chemotherapy Resistance 13 samples shares brca2, parp, chemotherapy, readthrough, restoration, resistance, inhibitor, specific
GSE212435 Targeting STAT3-FoxO1 axis reverses de novo and acquired PARP inhibitor resistance independent of BRCA status 31 samples shares parp, resistance, inhibitor
GSE281517 Lysosomal sequestration of PARP inhibitors drives heterogeneous accumulation in ovarian cancer to increase efficacy [RNA-seq] 72 samples shares parp, inhibitor
GSE222556 Neoadjuvant PARPi or Chemotherapy in Ovarian Cancer Informs Targeting Effector Treg Cells for Homologous-Recombination-Deficient Tumors [10x scRNA-seq] 67 samples shares parp, chemotherapy
GSE322780 PARP1 Suppression Drives ROS Resistance in Aneuploid Cancer Cells 46 samples shares parp, resistance
GSE288275 Inhibition of the STAT3/Fanconi anemia axis is synthetic lethal with PARP inhibitor in breast cancer 24 samples shares parp, inhibitor
GSE246085 Copper inhibits ATR and synergizes with PARP inhibitors (RNA-seq) 24 samples shares parp, inhibitor
GSE285827 PARP inhibitors differentially regulate immune responses in distinct genetic backgrounds of high-grade serous tubo-ovarian carcinoma 18 samples shares parp, inhibitor

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.