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NF1 modulates microtubular repair and dictates sensitivity to maytansinoid antibody-drug conjugates in HER2-positive breast cancer

GSE267855 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2024/12/01 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 18 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)
Topic
Breast cancerThis series is part of our curated briefing on it.
Samples
18 samples: 6 conditions, mostly in triplicateGroups 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)
NF1 is a tumor suppressor widely mutated across several cancers. Its best characterized function is the inhibition of RAS signaling through its GTPase-Activating Protein (GAP) domain. Additional functions have been proposed but not deeply investigated, due to its large size and complex domain structure. Here, combining patient data, in vitro/in vivo models and protein biochemistry, we show that NF1 is a novel Microtubule-Associated Protein (MAP) that modulates microtubular dynamics and intra-tubular repair.
Read the full summary ↓
NF1 loss results in mitotic defects such as prolonged mitosis, supranumerary centrosomes and chromosome missegregation, leading to low-grade aneuploidy in cell lines and patients. Loss of NF1-mediated intratubular repair creates a liability specifically targetable by maytansinoids, a class of microtubule-depolymerizing agents widely used as payloads in Antibody-Drug Conjugates such as Trastuzumab-Emtansine (T-DM1). Our results directly imply loss of intratubular repair as a driver of tumorigenesis, and NF1 as the first ADC payload-associated biomarker.
This dataset
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.

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 GSE267855_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1113536 and SRA study SRP508641. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
mock_ctrl ×3 mock_TDM1 ×3 NF1KO3_ctrl ×3 NF1KO3_TDM1 ×3 NF1KOAE6_ctrl ×3 NF1KOAE6_TDM1 ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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
More Breast cancer datasets

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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.