High resolution genome-wide SNP array analyses on matched colorectal-based lung and brain metastases

TL;DR

This study compares genetic changes in brain and lung metastases from colorectal cancer, finding more copy number variations and loss of heterozygosity in brain metastases.

Contribution

The study identifies previously unreported copy number variations and copy-neutral loss of heterozygosity regions specific to brain metastases in colorectal cancer.

Findings

Brain metastases had significantly more copy number variations (77) compared to lung metastases (24).

Twenty copy-neutral loss of heterozygosity regions were found exclusively in brain metastases, with 11 being previously unreported.

Specific genetic changes in brain metastases may influence signaling pathways like PI3K/AKT and transcriptional processes.

Abstract

Colorectal-based brain metastasis formation is a rare and late event in colorectal cancer (CRC) patients and is associated with poor survival. Compared with other metastatic sites, the knowledge about copy number variation (CNV) in brain metastases is still very limited. To get more information about CNVs, we applied SNP array to analyze chromosomal regions with a higher density of SNP markers.

Genome-wide high resolution single nucleotide polymorphism (SNP) array (CytoScan™ HD) analyses were carried out in matched colorectal-based lung and brain metastases of two patients.

Brain metastases harbored more CNVs (77 CNVs) than pulmonary metastases (24 CNVs). Not previously described specific CNVs were: gain of 1p36.33-p36.32, 4p16.3-p16.1, 6q27, 12q24.33, 16p13.3, as well as 16p12.1-p11.2 in lung metastases and gain of 1p36.33-p36.21, 5q11.1-q13.2, 21q22.2-q22.3, 22q11.21-q12.2, as well as 22q12.3-q13.33 in brain metastases.

Furthermore, we found 20 copy-neutral loss of heterozygosity (cn-LOH) regions exclusively in brain metastases, of which 11 cn-LOH regions have not been previously described.

Brain metastases of CRC showed more cn-LOH regions than lung metastases. Potentially affected genes within these regions could influence signaling pathways (e.g., PI3K/AKT signaling) as well as transcriptional processes. Perspectively, increased awareness of specific genetic characteristics can potentially increase the chance of early diagnosis of brain metastases, which could contribute to improved treatment options.

The online version contains supplementary material available at 10.1007/s00432-026-06427-7.

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