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

<p>Abstract</p> <p>Background</p> <p>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 i...

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Main Authors: Wessels Lodewyk F, Morreau Hans, Verwaal Victor J, van Beers Eric H, Joosse Simon A, Braaf Linde M, Liefers Gerrit-Jan, Klijn Christiaan, Bruin Sjoerd C, van Velthuysen Marie-Louise F, Tollenaar Rob AEM, van't Veer Laura J
Format: Article
Language:English
Published: BMC 2010-12-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/10/662
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author Wessels Lodewyk F
Morreau Hans
Verwaal Victor J
van Beers Eric H
Joosse Simon A
Braaf Linde M
Liefers Gerrit-Jan
Klijn Christiaan
Bruin Sjoerd C
van Velthuysen Marie-Louise F
Tollenaar Rob AEM
van't Veer Laura J
author_facet Wessels Lodewyk F
Morreau Hans
Verwaal Victor J
van Beers Eric H
Joosse Simon A
Braaf Linde M
Liefers Gerrit-Jan
Klijn Christiaan
Bruin Sjoerd C
van Velthuysen Marie-Louise F
Tollenaar Rob AEM
van't Veer Laura J
author_sort Wessels Lodewyk F
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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</p> <p>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).</p> <p>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</p> <p>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.</p> <p>Conclusion</p> <p>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>
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spelling doaj.art-85c81e0937014eb0a9a6f6e4f461d45f2022-12-21T22:01:38ZengBMCBMC Cancer1471-24072010-12-0110166210.1186/1471-2407-10-662Specific genomic aberrations in primary colorectal cancer are associated with liver metastasesWessels Lodewyk FMorreau HansVerwaal Victor Jvan Beers Eric HJoosse Simon ABraaf Linde MLiefers Gerrit-JanKlijn ChristiaanBruin Sjoerd Cvan Velthuysen Marie-Louise FTollenaar Rob AEMvan't Veer Laura J<p>Abstract</p> <p>Background</p> <p>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</p> <p>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).</p> <p>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</p> <p>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.</p> <p>Conclusion</p> <p>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>http://www.biomedcentral.com/1471-2407/10/662
spellingShingle Wessels Lodewyk F
Morreau Hans
Verwaal Victor J
van Beers Eric H
Joosse Simon A
Braaf Linde M
Liefers Gerrit-Jan
Klijn Christiaan
Bruin Sjoerd C
van Velthuysen Marie-Louise F
Tollenaar Rob AEM
van't Veer Laura J
Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
BMC Cancer
title Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
title_full Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
title_fullStr Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
title_full_unstemmed Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
title_short Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
title_sort specific genomic aberrations in primary colorectal cancer are associated with liver metastases
url http://www.biomedcentral.com/1471-2407/10/662
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