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Philippe Froguel - One of the best experts on this subject based on the ideXlab platform.

  • A Susceptibility Locus for Early-Onset Non-Insulin Dependent (Type 2) Diabetes Mellitus Maps to Chromosome 20q, Proximal to the Phosphoenolpyruvate Carboxykinase Gene
    Human molecular genetics, 1997
    Co-Authors: Habib Zouali, El Habib Hani, Anne Philippi, Nathalie Vionnet, Florence Demenais, Jacques S. Beckmann, Philippe Froguel
    Abstract:

    Several candidate genes for non-insulin-dependent diabetes mellitus (NIDDM) map on Chromosome 20, including the phosphoenolpyruvate carboxykinase gene (PCK1) and one of the maturity onset diabetes of the young genes (MODY1). Thus, we have investigated the entire long arm of Chromosome 20. Linkage analyses were conducted in a total sample of 148 NIDDM families (301 NIDDM sib pairs) and in a subset of 42 early onset NIDDM families, where genetic components are likely to play a more important role (55 NIDDM sib pairs diagnosed at or before 45 years of age), using 10 highly polymorphic markers with an average map density of 7.5 cM. Using affected sib pair methods (two-point linkage and multipoint linkage analyses), significant results were obtained with the 20q13 region, in the vicinity of the PCK1 locus, only in the subset of 55 early onset NIDDM sib pairs (multipoint MLS = 2.74, P = 0.0004; MLS = 2.34, P = 0.0009 when using a conservative weighting procedure). Moreover, another region spanning the ribophorin II (RPNII), phospholipase C (PLC1) and adenosine deaminase (ADA) loci suggested linkage with NIDDM (multipoint MLS of 1.81 in all NIDDM sib pairs, P= 0.003; MLS = 1.31, P = 0.012 when using a conservative weighting procedure). Whereas our study suggests the location of a susceptibility locus for early onset NIDDM in the PCK1 gene region, further investigation in larger data sets is required to confirm these results and assess the role of other regions on Chromosome 20q in human NIDDM.

  • indication for genetic linkage of the phosphoenolpyruvate carboxykinase pck1 gene region on Chromosome 20q to non insulin dependent diabetes mellitus
    Diabetes & Metabolism, 1996
    Co-Authors: El Habib Hani, Habib Zouali, Anne Philippi, Nathalie Vionnet, Philippe Passa, Florence Demenais, J C Beaudoin, Philippe Froguel
    Abstract:

    Le diabete non-insulino-dependant (DNID) est une maladie multifactorielle liee a l'interaction de plusieurs genes avec l'environnement. Il est cependant possible que certains genes puissent avoir un effet majeur dans le developpement du DNID, particulierement dans les formes familiales de diabete a debut precoce. Nous avons evalue par des etudes de liaison genetique, le role de quatre genes candidats potentiellement impliques dans l'insulino-resistance dans un echantillon de 55 familles multigenerationelles francaises d'origine caucasienne, en utilisant des analyses genetiques non parametriques (methodes des paires de germains affectes). Nous n'avons pas obtenu de liaison significative avec trois des genes etudies : glycogene synthase (GSY), substrat 1 au recepteur de l'insuline (IRS-1) et apolipoproteine C-II (APOC-II). Par contre, une liaison significative a ete retrouvee entre le DNID et le gene de la phosphoenolpyruvate carboxykinase (PCK1), localise sur le Chromosome 20q (p = 0.005 pour une proportion d'alleles transmis identiques par descendance, IBD = 0,55), et tout particulierement au sein des paires de germains affectes dont le DNID est apparu avant l'âge de 45 ans (p = 0,0003, IBD = 0,66). Ces resultats suggerent la contribution du gene PCK1 ou d'un autre gene proche de PCK1 au developpement du DNID dans la population francaise.

  • Indication for genetic linkage of the phosphoenolpyruvate carboxykinase (PCK1) gene region on Chromosome 20q to non-insulin-dependent diabetes mellitus.
    Diabetes & metabolism, 1996
    Co-Authors: El Habib Hani, Habib Zouali, Anne Philippi, Nathalie Vionnet, Philippe Passa, Florence Demenais, Philippe Froguel
    Abstract:

    There is strong evidence that non-insulin-dependent-diabetes mellitus (NIDDM) has a polygenic mode of inheritance. Nevertheless, major gene effects may be involved in its pathogenesis, especially in forms with an early age of onset. We performed linkage analyses between 4 candidate genes for insulin resistance and NIDDM in a set of 55 multigenerational French Caucasian families, using the affected sib-pair approach. No significant results were obtained with glycogen synthase (GSY), insulin receptor substrate-1 (IRS-1) and apolipoprotein C-II (APOC-II) genes. However, a significant trend towards linkage was found between NIDDM and the phosphoenolpyruvate carboxykinase gene (PCK1) located on Chromosome 20q (p = 0.005 for the mean estimated proportion of alleles shared identically by descent, mean IBD = 0.55), particularly among sib-pairs with diabetes diagnosed before the age of 46 years (p = 0.0003, mean IBD = 0.66). These results suggest that the PCK1 gene or a nearby locus contributes to the development of NIDDM in the French population.

  • A gene for maturity onset diabetes of the young (MODY) maps to Chromosome 12q.
    Nature genetics, 1995
    Co-Authors: Martine Vaxillaire, Philippe Passa, Jacques S. Beckmann, Valérie Boccio, A. Philippi, C. Vigouroux, Joseph D. Terwilliger, Gilberto Velho, G. M. Lathrop, Philippe Froguel
    Abstract:

    Maturity–onset diabetes of the young (MODY) is a subtype of non–insulin dependent diabetes mellitus, with early age of onset. MODY is genetically heterogeneous, associated with glucokinase mutations and a locus on Chromosome 20q; in about 50% of cases, its genetic background is unknown. We have studied 12 families in which MODY is unlinked to either glucokinase or Chromosome 20q markers, and find significant evidence for linkage with microsatellite markers on Chromosome 12q, most likely within a 7 centimorgan interval bracketed by D12S86 and D12S342. The disease was estimated to be linked to this Chromosome region in approximately 50% of families in a heterogeneity analysis. These MODY patients exhibit major hyperglycaemia with a severe insulin secretory defect, suggesting that the causal gene is implicated in pancreatic β–cell function.

  • Maturity-onset diabetes of the young.
    Current opinion in pediatrics, 1994
    Co-Authors: Philippe Froguel, Gilberto Velho
    Abstract:

    Maturity-onset diabetes of the young (MODY) is an autosomal dominant-subtype of noninsulin-dependent diabetes mellitus, characterized by an early age of onset. MODY is considered a model for genetic studies of noninsulin-dependent diabetes mellitus because of the availability of large multigenerational families, which make linkage analyses possible. So far, two MODY susceptibility loci have been reported, one unknown gene on Chromosome 20q, and glucokinase on Chromosome 7q. Glucokinase mutations appear to be the most common cause of MODY in the European population, being found in 60% of the families investigated. This form of diabetes results from a primary defect in insulin secretion due to the reduced enzymatic activity of the mutant glucokinase. The search for a third MODY gene will provide a better understanding of diabetes in childhood.

Harald Juppner - One of the best experts on this subject based on the ideXlab platform.

  • Pseudohypoparathyroidism type 1B caused by methylation changes at the GNAS complex locus
    BMJ case reports, 2016
    Co-Authors: Sabrina Poradosu, Rieko Takatani, Bert Bravenboer, Harald Juppner
    Abstract:

    Pseudohypoparathyroidism type 1B (PHP1B) consists of a heterogeneous group of disorders characterised by resistance to parathyroid hormone (PTH). There are several different PHP1B subtypes that are all associated with methylation changes at GNAS. These epigenetic changes are caused by maternal deletions in GNAS or STX16, by paternal uniparental isodisomy of Chromosome 20q (patUPD20q) or by undefined genetic mutations. The GNAS methylation changes are ultimately responsible for resistance to PTH signalling in the proximal renal tubules. However, there is no PTH resistance in the distal renal tubules nor in bone cells; consequently, patients with PHP1B have reduced urinary calcium excretion and can readily mobilise calcium (and phosphate) from the skeleton. We report a case of a sporadic PHP1B patient with broad GNAS methylation changes that were presumably caused by an unknown genetic mutation outside the GNAS locus. PTH resistance was preceded by several years by autoimmune negative hypothyroidism. Treatment consisted of calcium substitution and calcitriol.

  • pseudohypoparathyroidism type ib php ib pth resistant hypocalcemia and hyperphosphatemia due to abnormal gnas methylation
    2015
    Co-Authors: Harald Juppner
    Abstract:

    Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare disorder characterized by PTH resistance in the proximal renal tubules, which leads to hypocalcemia, hyperphosphatemia, and an elevated serum PTH level. Resistance to other hormones that mediate their actions through G protein-coupled receptors and evidence for AHO can also be observed but are much less frequently than in pseudohypoparathyroidism type Ia (PHP-Ia). Most variants of PHP-Ib are associated with GNAS methylation changes, thereby reducing maternal expression of the stimulatory G protein (Gsα) in few tissues, where paternal expression of this signaling protein is silenced through as-of-yet unknown mechanisms. In familial PHP-Ib cases, these epigenetic changes are caused by deletions within or upstream of GNAS. Duplication of large portions of the paternal Chromosome 20q is observed in a few patients with the sporadic form of the disease, but most of these PHP-Ib cases remain undefined at the molecular level.

  • paternal uniparental isodisomy of Chromosome 20q and the resulting changes in gnas1 methylation as a plausible cause of pseudohypoparathyroidism
    American Journal of Human Genetics, 2001
    Co-Authors: Murat Bastepe, Andrew Lane, Harald Juppner
    Abstract:

    Heterozygous inactivating mutations in the GNAS1 exons (20q13.3) that encode the α-subunit of the stimulatory G protein (Gsα) are found in patients with pseudohypoparathyroidism type Ia (PHP-Ia) and in patients with pseudo-pseudohypoparathyroidism (pPHP). However, because of paternal imprinting, resistance to parathyroid hormone (PTH)—and, sometimes, to other hormones that require Gsα signaling—develops only if the defect is inherited from a female carrier of the disease gene. An identical mode of inheritance is observed in kindreds with pseudohypoparathyroidism type Ib (PHP-Ib), which is most likely caused by mutations in regulatory regions of the maternal GNAS1 gene that are predicted to interfere with the parent-specific methylation of this gene. We report a patient with PTH-resistant hypocalcemia and hyperphosphatemia but without evidence for Albright hereditary osteodystrophy who has paternal uniparental isodisomy of Chromosome 20q and lacks the maternal-specific methylation pattern within GNAS1. Since studies in the patient’s fibroblasts did not reveal any evidence of impaired Gsα protein or activity, it appears that the loss of the maternal GNAS1 gene and the resulting epigenetic changes alone can lead to PTH resistance in the proximal renal tubules and thus lead to impaired regulation of mineral-ion homeostasis.

  • Paternal Uniparental Isodisomy of Chromosome 20q—and the Resulting Changes in GNAS1 Methylation—as a Plausible Cause of Pseudohypoparathyroidism
    American journal of human genetics, 2001
    Co-Authors: Murat Bastepe, Andrew H. Lane, Harald Juppner
    Abstract:

    Heterozygous inactivating mutations in the GNAS1 exons (20q13.3) that encode the alpha-subunit of the stimulatory G protein (Gsalpha) are found in patients with pseudohypoparathyroidism type Ia (PHP-Ia) and in patients with pseudo-pseudohypoparathyroidism (pPHP). However, because of paternal imprinting, resistance to parathyroid hormone (PTH)-and, sometimes, to other hormones that require Gsalpha signaling-develops only if the defect is inherited from a female carrier of the disease gene. An identical mode of inheritance is observed in kindreds with pseudohypoparathyroidism type Ib (PHP-Ib), which is most likely caused by mutations in regulatory regions of the maternal GNAS1 gene that are predicted to interfere with the parent-specific methylation of this gene. We report a patient with PTH-resistant hypocalcemia and hyperphosphatemia but without evidence for Albright hereditary osteodystrophy who has paternal uniparental isodisomy of Chromosome 20q and lacks the maternal-specific methylation pattern within GNAS1. Since studies in the patient's fibroblasts did not reveal any evidence of impaired Gsalpha protein or activity, it appears that the loss of the maternal GNAS1 gene and the resulting epigenetic changes alone can lead to PTH resistance in the proximal renal tubules and thus lead to impaired regulation of mineral-ion homeostasis.

  • the gene responsible for pseudohypoparathyroidism type ib is paternally imprinted and maps in four unrelated kindreds to Chromosome 20q13 3
    Proceedings of the National Academy of Sciences of the United States of America, 1998
    Co-Authors: Harald Juppner, Margaret L Lawson, H Plotkin, Michael Mannstadt, David E C Cole, Hiroyuki Koshiyama, Murat Bastepe, Geoffrey N. Hendy, Ernestina Schipani, J D Crawford
    Abstract:

    Hypocalcemia and hyperphosphatemia caused by parathyroid hormone (PTH)-resistance are the only discernible abnormalities in pseudohypoparathyroidism type Ib (PHP-Ib). Because mutations in the PTH/PTH-related peptide receptor, a plausible candidate gene, had been excluded previously, we conducted a genome-wide search with four PHP-Ib kindreds and established linkage to a small telomeric region on Chromosome 20q, which contains the stimulatory G protein gene. We, furthermore, showed that the genetic defect is imprinted paternally and thus is inherited in the same mode as the PTH-resistant hypocalcemia in kindreds with PHP-Ia and/or pseudo-pseudohypoparathyroidism, two related disorders caused by different stimulatory G protein mutations.

Jiajing Wang - One of the best experts on this subject based on the ideXlab platform.

  • Chromosome 20q amplification defines a subtype of microsatellite stable left sided colon cancers with wild type ras raf and better overall survival
    Molecular Cancer Research, 2017
    Co-Authors: Ryan Ptashkin, Carlos Pagan, Rona Yaeger, Sumit Middha, Jinru Shia, Michael F. Berger, Lu Wang, Robert Cimera, Kevin P Orourke, Jiajing Wang
    Abstract:

    Here, comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma harboring Chromosome 20q amplification. Tumor and normal DNA from patients with advanced colorectal carcinoma underwent next-generation sequencing via MSK-IMPACT, and a subset of case samples was subjected to high-resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) colorectal carcinoma data. Of the colorectal carcinoma patients sequenced (n = 401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification. In both the MSK-IMPACT and TCGA datasets, BCL2L1 was the most frequently amplified 20q oncogene. However, SRC was the only recognized 20q oncogene with a significant inverse relationship between mRNA upregulation and RAS/RAF mutation (OR, -0.4 ± 0.2, P = 0.02). In comparison with 20q diploid colorectal carcinoma, 20q gain/amplification was associated with wild-type KRAS (P < 0.001) and BRAF (P = 0.01), microsatellite stability (P < 0.001), distal primary tumors (P < 0.001), and mutant TP53 (P < 0.001), but not stage. On multivariate analysis, longer overall survival from the date of metastasis was observed with Chromosome 20q gain (P = 0.02) or amplification (P = 0.04) compared with diploid 20q.Implications: 20q amplification defines a subset of colorectal cancer patients with better overall survival from the date of metastasis, and further studies are warranted to assess whether the inhibition of 20q oncogenes, such as SRC, may benefit this subset of patients. Mol Cancer Res; 15(6); 708-13. ©2017 AACR.

  • Chromosome 20q Amplification Defines a Subtype of Microsatellite Stable, Left-Sided Colon Cancers with Wild-type RAS/RAF and Better Overall Survival.
    Molecular cancer research : MCR, 2017
    Co-Authors: Ryan Ptashkin, Carlos Pagan, Rona Yaeger, Sumit Middha, Jinru Shia, Kevin P. O’rourke, Michael F. Berger, Lu Wang, Robert Cimera, Jiajing Wang
    Abstract:

    Here, comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma harboring Chromosome 20q amplification. Tumor and normal DNA from patients with advanced colorectal carcinoma underwent next-generation sequencing via MSK-IMPACT, and a subset of case samples was subjected to high-resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) colorectal carcinoma data. Of the colorectal carcinoma patients sequenced (n = 401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification. In both the MSK-IMPACT and TCGA datasets, BCL2L1 was the most frequently amplified 20q oncogene. However, SRC was the only recognized 20q oncogene with a significant inverse relationship between mRNA upregulation and RAS/RAF mutation (OR, -0.4 ± 0.2, P = 0.02). In comparison with 20q diploid colorectal carcinoma, 20q gain/amplification was associated with wild-type KRAS (P < 0.001) and BRAF (P = 0.01), microsatellite stability (P < 0.001), distal primary tumors (P < 0.001), and mutant TP53 (P < 0.001), but not stage. On multivariate analysis, longer overall survival from the date of metastasis was observed with Chromosome 20q gain (P = 0.02) or amplification (P = 0.04) compared with diploid 20q.Implications: 20q amplification defines a subset of colorectal cancer patients with better overall survival from the date of metastasis, and further studies are warranted to assess whether the inhibition of 20q oncogenes, such as SRC, may benefit this subset of patients. Mol Cancer Res; 15(6); 708-13. ©2017 AACR.

Stephen C. L. Gough - One of the best experts on this subject based on the ideXlab platform.

  • a single nucleotide polymorphism in the cd40 gene on Chromosome 20q gd 2 provides no evidence for susceptibility to graves disease in uk caucasians
    Clinical Endocrinology, 2004
    Co-Authors: Joanne M. Heward, Matthew J. Simmonds, Helen Foxall, Jayne A. Franklyn, Jackie Carrsmith, Stephen C. L. Gough
    Abstract:

    Summary objective  A genome-wide screen in Graves’ disease (GD) has shown linkage to Chromosome 20q, designated GD-2. The gene encoding CD40, which stimulates lymphocyte proliferation and differentiation, maps to this region, and a single nucleotide polymorphism (SNP) at position −1 of the Kozak sequence within the gene has been reported to be associated with GD. The aim of this study was to determine whether this SNP of the CD40 gene confers susceptibility to GD in UK Caucasians. design  A large case–control cohort consisting of 800 patients with GD, and 785 control subjects with no history of autoimmune disease, was used to genotype this SNP by polymerase chain reaction restriction fragment length polymorphism. results  Despite adequate power (> 99%) to detect an effect, if present (odds ratio of 1·5), no significant difference in allele or genotype frequency of the CD40 SNP was observed between patients with GD and control subjects (P = 0·087 and P = 0·145, respectively). conclusions  These data suggest that this polymorphism of the CD40 gene is not associated with GD in the UK and is therefore not contributing to disease susceptibility in the chromosomal region designated GD-2.

  • A single nucleotide polymorphism in the CD40 gene on Chromosome 20q (GD-2) provides no evidence for susceptibility to Graves' disease in UK Caucasians
    Clinical endocrinology, 2004
    Co-Authors: Joanne M. Heward, Matthew J. Simmonds, Jackie Carr-smith, Helen Foxall, Jayne A. Franklyn, Stephen C. L. Gough
    Abstract:

    A genome-wide screen in Graves' disease (GD) has shown linkage to Chromosome 20q, designated GD-2. The gene encoding CD40, which stimulates lymphocyte proliferation and differentiation, maps to this region, and a single nucleotide polymorphism (SNP) at position -1 of the Kozak sequence within the gene has been reported to be associated with GD. The aim of this study was to determine whether this SNP of the CD40 gene confers susceptibility to GD in UK Caucasians. A large case-control cohort consisting of 800 patients with GD, and 785 control subjects with no history of autoimmune disease, was used to genotype this SNP by polymerase chain reaction restriction fragment length polymorphism. Despite adequate power (> 99%) to detect an effect, if present (odds ratio of 1.5), no significant difference in allele or genotype frequency of the CD40 SNP was observed between patients with GD and control subjects (P = 0.087 and P = 0.145, respectively). These data suggest that this polymorphism of the CD40 gene is not associated with GD in the UK and is therefore not contributing to disease susceptibility in the chromosomal region designated GD-2.

M-l F Van Velthuysen - One of the best experts on this subject based on the ideXlab platform.

  • Molecular alterations associated with liver metastases development in colorectal cancer patients
    British journal of cancer, 2011
    Co-Authors: Sjoerd C. Bruin, I. Mikolajewska-hanclich, G.j. Liefers, Christiaan Klijn, Andrew Vincent, Victor J. Verwaal, K A De Groot, Hans Morreau, M-l F Van Velthuysen
    Abstract:

    Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases. Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n=39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n=46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n=48). All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. The primary CRCs of the LM group had significantly higher frequency of amplified Chromosome 20q (P=0.003), significantly fewer mutations in the PI(3)K signalling pathway (P=0.003) and fewer CIMP high tumours (P=0.05). There was a strong inverse correlation between 20q and the PI(3)K pathway mutations. The development of CRC liver metastases is associated with amplification of Chromosome 20q and not driven by mutations in the PI(3)K signalling pathway.

  • Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
    BMC cancer, 2010
    Co-Authors: Sjoerd C. Bruin, G.j. Liefers, Christiaan Klijn, Victor J. Verwaal, Hans Morreau, Linde M. Braaf, Simon A. Joosse, Eric H. Van Beers, Lodewyk F. A. Wessels, M-l F Van Velthuysen
    Abstract:

    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. 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). 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. 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.

  • Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
    Lung Cancer, 2010
    Co-Authors: Sjoerd C. Bruin, G.j. Liefers, Christiaan Klijn, Victor J. Verwaal, Hans Morreau, Linde M. Braaf, Simon A. Joosse, Eric H. Van Beers, Lodewyk F. A. Wessels, M-l F Van Velthuysen
    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 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.