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Specific genomic aberrations in primary colorectal cancer are associated with liver metastases

Bruin, Sjoerd C ; Klijn, Christiaan ; Liefers, Gerrit-Jan ; Braaf, Linde M ; Joosse, Simon A ; van Beers, Eric H ; Verwaal, Victor J LU ; Morreau, Hans ; Wessels, Lodewyk F and van Velthuysen, Marie-Louise F , et al. (2010) In BMC Cancer 10. p.1-12
Abstract

BACKGROUND: Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal signature for organ specific metastases.

METHODS: Array Comparative Genomic Hybridization (aCGH) was employed to asses DNA copy number changes in primary colorectal tumors of three distinctive patient groups. This included formalin-fixed, paraffin-embedded tissue of patients who developed liver metastases (LM; n = 36), metastases (PM; n = 37) and a group that remained metastases-free (M0; n = 25).A novel statistical method for identifying... (More)

BACKGROUND: Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal signature for organ specific metastases.

METHODS: Array Comparative Genomic Hybridization (aCGH) was employed to asses DNA copy number changes in primary colorectal tumors of three distinctive patient groups. This included formalin-fixed, paraffin-embedded tissue of patients who developed liver metastases (LM; n = 36), metastases (PM; n = 37) and a group that remained metastases-free (M0; n = 25).A novel statistical method for identifying recurrent copy number changes, KC-SMART, was used to find specific locations of genomic aberrations specific for various groups. We created a classifier for organ specific metastases based on the aCGH data using Prediction Analysis for Microarrays (PAM).

RESULTS: Specifically in the tumors of primary CRC patients who subsequently developed liver metastasis, KC-SMART analysis identified genomic aberrations on chromosome 20q. LM-PAM, a shrunken centroids classifier for liver metastases occurrence, was able to distinguish the LM group from the other groups (M0&PM) with 80% accuracy (78% sensitivity and 86% specificity). The classification is predominantly based on chromosome 20q aberrations.

CONCLUSION: Liver specific CRC metastases may be predicted with a high accuracy based on specific genomic aberrations in the primary CRC tumor. The ability to predict the site of metastases is important for improvement of personalized patient management.

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publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Aged, Chi-Square Distribution, Chromosome Aberrations, Chromosomes, Human, Pair 20, Colorectal Neoplasms/genetics, Comparative Genomic Hybridization, Databases, Genetic, Female, Fixatives, Formaldehyde, Gene Dosage, Gene Expression Profiling/methods, Genetic Predisposition to Disease, Humans, Liver Neoplasms/genetics, Logistic Models, Male, Middle Aged, Neoplasm Staging, Netherlands, Oligonucleotide Array Sequence Analysis, Paraffin Embedding, Phenotype, Predictive Value of Tests, Survival Analysis, Time Factors, Tissue Fixation/methods, Treatment Outcome
in
BMC Cancer
volume
10
article number
662
pages
1 - 12
publisher
BioMed Central (BMC)
external identifiers
  • scopus:78649556558
  • pmid:21126340
ISSN
1471-2407
DOI
10.1186/1471-2407-10-662
language
English
LU publication?
no
id
c6c01116-3075-47a3-b6c5-c5e0d057bac3
date added to LUP
2022-04-05 11:18:18
date last changed
2024-01-03 09:41:21
@article{c6c01116-3075-47a3-b6c5-c5e0d057bac3,
  abstract     = {{<p>BACKGROUND: Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal signature for organ specific metastases.</p><p>METHODS: Array Comparative Genomic Hybridization (aCGH) was employed to asses DNA copy number changes in primary colorectal tumors of three distinctive patient groups. This included formalin-fixed, paraffin-embedded tissue of patients who developed liver metastases (LM; n = 36), metastases (PM; n = 37) and a group that remained metastases-free (M0; n = 25).A novel statistical method for identifying recurrent copy number changes, KC-SMART, was used to find specific locations of genomic aberrations specific for various groups. We created a classifier for organ specific metastases based on the aCGH data using Prediction Analysis for Microarrays (PAM).</p><p>RESULTS: Specifically in the tumors of primary CRC patients who subsequently developed liver metastasis, KC-SMART analysis identified genomic aberrations on chromosome 20q. LM-PAM, a shrunken centroids classifier for liver metastases occurrence, was able to distinguish the LM group from the other groups (M0&amp;PM) with 80% accuracy (78% sensitivity and 86% specificity). The classification is predominantly based on chromosome 20q aberrations.</p><p>CONCLUSION: Liver specific CRC metastases may be predicted with a high accuracy based on specific genomic aberrations in the primary CRC tumor. The ability to predict the site of metastases is important for improvement of personalized patient management.</p>}},
  author       = {{Bruin, Sjoerd C and Klijn, Christiaan and Liefers, Gerrit-Jan and Braaf, Linde M and Joosse, Simon A and van Beers, Eric H and Verwaal, Victor J and Morreau, Hans and Wessels, Lodewyk F and van Velthuysen, Marie-Louise F and Tollenaar, Rob A E M and Van't Veer, Laura J}},
  issn         = {{1471-2407}},
  keywords     = {{Adult; Aged; Chi-Square Distribution; Chromosome Aberrations; Chromosomes, Human, Pair 20; Colorectal Neoplasms/genetics; Comparative Genomic Hybridization; Databases, Genetic; Female; Fixatives; Formaldehyde; Gene Dosage; Gene Expression Profiling/methods; Genetic Predisposition to Disease; Humans; Liver Neoplasms/genetics; Logistic Models; Male; Middle Aged; Neoplasm Staging; Netherlands; Oligonucleotide Array Sequence Analysis; Paraffin Embedding; Phenotype; Predictive Value of Tests; Survival Analysis; Time Factors; Tissue Fixation/methods; Treatment Outcome}},
  language     = {{eng}},
  pages        = {{1--12}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Cancer}},
  title        = {{Specific genomic aberrations in primary colorectal cancer are associated with liver metastases}},
  url          = {{http://dx.doi.org/10.1186/1471-2407-10-662}},
  doi          = {{10.1186/1471-2407-10-662}},
  volume       = {{10}},
  year         = {{2010}},
}