Focus on 16p13.3 Locus in Colon Cancer

Abstract

BackgroundWith 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.Materials and MethodsIn 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.ResultsBoth 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.ConclusionsIn conclusion, copy number variation of the 16p13.3 locus seems to be an important parameter for prediction of disease recurrence in colon cancer.

Genomic Gain of 16p13.3 in Prostate Cancer Predicts Poor Clinical Outcome after Surgical Intervention

“…The association of 16p13.3 gain with features of aggressive tumors was in line with studies in the breast (33), lung (34), and colon cancer (35), wherein the 16p13 gain was linked to poor prognosis. Our previous study defined the minimal region of 16p13.3 gain spanning 19 genes.…”

Unexpected frequency of genomic alterations in histologically normal colonic tissue from colon cancer patients

“…For example, in tumoral tissues, we found two gained regions shared among at least three samples and containing RBFOX1 and PCDH11Y genes. RBFOX1 belongs to a family of evolutionarily conserved RNA-binding proteins and regulates tissue-specific alternative splicing: deletion of RBFOX1 has been already reported in colon tumors [28] whereas copy number gain has been recently shown [29]. PCDH11Y instead plays a role during development of the central nervous system, but it has also been reported to be involved in prostate cancer progression [30].…”

Peroxiredoxin 1 – an antioxidant enzyme in cancer

“…Li R et al found that elevated expression of PRDX1 is characterized of both increased DNA copy number and increased transcript levels in lung adenocarcinoma [41]. Recurrent gains were found for chromosome 1q in colorectal cancer [47,48]. PRDX1 was obviously amplified in colorectal primary tumours compared with normal colon samples by the significance analysis of microarrays [43].…”