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Focus on 16p13.3 Locus in Colon Cancer.

Mampaey E, Fieuw A, Van Laethem T, Ferdinande L, Claes K, Ceelen W, Van Nieuwenhove Y, Pattyn P, De Man M, De Ruyck K, Van Roy N, Geboes K, Laurent S - PLoS ONE (2015)

Bottom Line: 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.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.In conclusion, copy number variation of the 16p13.3 locus seems to be an important parameter for prediction of disease recurrence in colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology-Digestive Oncology, Ghent University Hospital, Ghent, Belgium.

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.

Materials and 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.

No MeSH data available.


Related in: MedlinePlus

Kaplan Meier survival curves represented a worse prognosis for patients with loss of chromosome 4.Loss of chromosome 4 is linked with a shorter RFS, ***P<0,001 (A) and a smaller 2-year OS, **P = 0,002 (B). Patients without an alteration of chromosome 4 are presented in green, those with loss of chromosome 4 in blue.
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pone.0131421.g003: Kaplan Meier survival curves represented a worse prognosis for patients with loss of chromosome 4.Loss of chromosome 4 is linked with a shorter RFS, ***P<0,001 (A) and a smaller 2-year OS, **P = 0,002 (B). Patients without an alteration of chromosome 4 are presented in green, those with loss of chromosome 4 in blue.

Mentions: Array comparative genomic hybridization (array-CGH) analysis showed that the most frequent CNAs in colon carcinomas were gains of chromosomes 1q, 7, 8q, 13, 20 and 20q and losses of chromosomes 1p, 4, 8p, 14, 15, 17p, 18, 21 and 22 (Fig 1). We also found the presence of multiple isochromosomes in our samples for chromosomes 1, 5 and 8 (respectively in 5.4%, 5.4% and 7.5% of our patients). Loss of chromosome 4 was significantly linked to a shorter RFS (mean RFS is 241.7 weeks for patients with a loss of chromosome 4 and 433.96 weeks for patients without chromosome 4 loss, ***P<0.001) (Fig 3A). Loss of chromosome 1, 3, 4 and 9 were linked to a shorter 2-year OS (respectively P = 0.053, **P = 0.005, **P = 0.002 and P = 0.069) (Fig 3B and Figures A-C in S4 File). Gain of chromosome 7 and 20 was shown to be significantly linked with a better 2-year OS (respectively *P = 0.048 and *P = 0.035) (Figures D-E in S4 File).


Focus on 16p13.3 Locus in Colon Cancer.

Mampaey E, Fieuw A, Van Laethem T, Ferdinande L, Claes K, Ceelen W, Van Nieuwenhove Y, Pattyn P, De Man M, De Ruyck K, Van Roy N, Geboes K, Laurent S - PLoS ONE (2015)

Kaplan Meier survival curves represented a worse prognosis for patients with loss of chromosome 4.Loss of chromosome 4 is linked with a shorter RFS, ***P<0,001 (A) and a smaller 2-year OS, **P = 0,002 (B). Patients without an alteration of chromosome 4 are presented in green, those with loss of chromosome 4 in blue.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4519182&req=5

pone.0131421.g003: Kaplan Meier survival curves represented a worse prognosis for patients with loss of chromosome 4.Loss of chromosome 4 is linked with a shorter RFS, ***P<0,001 (A) and a smaller 2-year OS, **P = 0,002 (B). Patients without an alteration of chromosome 4 are presented in green, those with loss of chromosome 4 in blue.
Mentions: Array comparative genomic hybridization (array-CGH) analysis showed that the most frequent CNAs in colon carcinomas were gains of chromosomes 1q, 7, 8q, 13, 20 and 20q and losses of chromosomes 1p, 4, 8p, 14, 15, 17p, 18, 21 and 22 (Fig 1). We also found the presence of multiple isochromosomes in our samples for chromosomes 1, 5 and 8 (respectively in 5.4%, 5.4% and 7.5% of our patients). Loss of chromosome 4 was significantly linked to a shorter RFS (mean RFS is 241.7 weeks for patients with a loss of chromosome 4 and 433.96 weeks for patients without chromosome 4 loss, ***P<0.001) (Fig 3A). Loss of chromosome 1, 3, 4 and 9 were linked to a shorter 2-year OS (respectively P = 0.053, **P = 0.005, **P = 0.002 and P = 0.069) (Fig 3B and Figures A-C in S4 File). Gain of chromosome 7 and 20 was shown to be significantly linked with a better 2-year OS (respectively *P = 0.048 and *P = 0.035) (Figures D-E in S4 File).

Bottom Line: 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.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.In conclusion, copy number variation of the 16p13.3 locus seems to be an important parameter for prediction of disease recurrence in colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology-Digestive Oncology, Ghent University Hospital, Ghent, Belgium.

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.

Materials and 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.

No MeSH data available.


Related in: MedlinePlus