title: Focus on 16p13.3 Locus in Colon Cancer.
abstract: BACKGROUND
  With one million new cases of colorectal cancer (CRC) diagnosed annually in the world, CRC is the third most commonly diagnosed cancer in the Western world. Patients with stage I-III CRC can be cured with surgery but are at risk for recurrence. Colorectal cancer is characterized by the presence of chromosomal deletions and gains. Large genomic profiling studies have however not been conducted in this disease. The number of a specific genetic aberration in a tumour sample could correlate with recurrence-free survival or overall survival, possibly leading to its use as biomarker for therapeutic decisions. At this point there are not sufficient markers for prediction of disease recurrence in colorectal cancer, which can be used in the clinic to discriminate between stage II patients who will benefit from adjuvant chemotherapy. For instance, the benefit of adjuvant chemotherapy has been most clearly demonstrated in stage III disease with an approximately 30 percent relative reduction in the risk of disease recurrence. The benefits of adjuvant chemotherapy in stage II disease are less certain, the risk for relapse is much smaller in the overall group and the specific patients at risk are hard to identify.
  
  
  METHODS
  In this study, array-comparative genomic hybridization analysis (array-CGH) was applied to study high-resolution DNA copy number alterations in 93 colon carcinoma samples. These genomic data were combined with parameters like KRAS mutation status, microsatellite status and clinicopathological characteristics.
  
  
  RESULTS
  Both large and small chromosomal losses and gains were identified in our sample cohort. Recurrent gains were found for chromosome 1q, 7, 8q, 13 and 20 and losses were mostly found for 1p, 4, 8p, 14, 15, 17p, 18, 21 and 22. Data analysis demonstrated that loss of chromosome 4 is linked to a worse prognosis in our patients series. Besides these alterations, two interesting small regions of overlap were identified, which could be associated with disease recurrence. Gain of the 16p13.3 locus (including the RNA binding protein, fox-1 homolog gene, RBFOX1) was linked with a worse recurrence-free survival in our patient cohort. On the other hand, loss of RBFOX1 was only found in patients without disease recurrence. Most interestingly, above mentioned characteristics were also found in stage II patients, for whom there is a high medical need for the identification of new prognostic biomarkers.
  
  
  CONCLUSIONS
  In conclusion, copy number variation of the 16p13.3 locus seems to be an important parameter for prediction of disease recurrence in colon cancer.
authors.affiliation: Department of Gastroenterology-Digestive Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Evi
authors.initials: E
authors.lastname: Mampaey
authors.affiliation: Department of Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Fieuw
authors.affiliation: Department of Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Thalia
authors.initials: T
authors.lastname: Van Laethem
authors.affiliation: Department of Pathology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Ferdinande
authors.affiliation: Department of Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.affiliation: Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Ceelen
authors.affiliation: Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Van Nieuwenhove
authors.affiliation: Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Pattyn
authors.affiliation: Department of Gastroenterology-Digestive Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: De Man
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: De Ruyck
authors.affiliation: Department of Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.affiliation: Department of Gastroenterology-Digestive Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Geboes
authors.affiliation: Department of Gastroenterology-Digestive Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Laurent
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002869:Chromosome Aberrations; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D056426:Genetic Loci; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins