GEO series

Spectrum, clinical correlates and clinical implications of BRAF-inhibitor resistance mechanisms in melanoma

GSE50509 Homo sapiens (human) Expression microarray 61 samples Submitted 2014/02/19 Platform GPL10558

At a glance

Expression microarray · human · 61 samples

What it is: Expression microarrayGene activity read on a chip (the older technology that RNA-seq replaced).
Organism: Homo sapiens (human)
Topic: MelanomaThis series is part of our curated briefing on it.
Samples: 61 samples
Data you can get: A processed expression table (series matrix) and the array files, from NCBI.

Summary (written by the submitters)

Multiple BRAF inhibitor resistance mechanisms have been described, however their relative frequency, clinical correlates, and effect on subsequent therapy have not been assessed in patients with metastatic melanoma. Excised progressing BRAFV600 mutant melanoma metastases (Prog) from patients treated with dabrafenib (n=22) or vemurafenib (n=8) were analyzed for known resistance mechanisms.

Read the full summary ↓

Oncogenic signaling in Prog and matched pre-treatment tumors was examined using gene expression analysis. Resistance mechanisms were correlated with clinicopathologic features and outcome. A resistance mechanism was identified in 21/38 (55%) Prog samples from 30 patients; BRAF splice variants (n=12, 32%), N-RAS mutations (n=3, 8%), BRAF amplification (n=3, 8%), MEK1/2 mutations (n=3, 8%) and an AKT1 mutation (n=1, 3%). Four Progs tumours displayed multiple resistance mechanisms, and four patients with multiple Progs demonstrated inter-tumoral heterogeneity of resistance mechanisms. Six (21%) of 29 Progs showed loss of MAPK activity by gene expression analysis. These MAPK-inhibited Progs had unknown resistance mechanisms, and these patients had a shorter progression-free survival than patients with MAPK re-activated Progs. There were no responses to subsequent targeted therapy, even when the identified mechanism of resistance was predicted to be responsive. Heterogeneity of resistance mechanisms was common between patients, within patients and within individual tumors. The MAPK pathway remained inhibited in a subset of resistant tumors with unknown mechanisms of resistance, and the outcomes of patients with these tumors are poor. The use of sequential targeted therapies based on the molecular characteristics of a single progressing biopsy is unlikely to provide improved clinical outcomes.

This dataset

Open GSE50509 in finder → Find more human microarray datasets → Melanoma landscape →

Download · which file do I need?

Direct links to NCBI, 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.

All supplementary files ↗

3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE50509_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Whole study · RAW.tar ↓

What the files usually look like: For arrays the series matrix is normally the normalised expression table you want; the raw array files (CEL and similar) are in the RAW.tar.

Also filed as BioProject PRJNA218009. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 24463458) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 61 more — browse all 61 samples with per-sample file links →

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