p16INK4a polymorphism: associations with tumour progression in patients with sporadic colorectal cancer

McCloud, Jonathan M.; Sivakumar, Rangasamy; Greenhough, Alexander; Elder, Jackie; Jones, Peter W.; Deakin, Mark; Elder, J. Bradley; Fryer, Anthony A.; Hoban, Paul R.

doi:10.3892/ijo.25.5.1447

Cited by 11 publications

(13 citation statements)

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“…These SNPs have been phenotypically associated with solid tumors such as nonHodgkin lymphoma (33), breast cancer (34), colorectal cancer (35), and other diseases, such as Alzheimer's (36) and melanoma (37). However, their role in leukemia has not yet been well established and a larger number of patients is required to show any potential association.…”

Section: Discussionmentioning

confidence: 99%

CDKN2A/BAlterations Impair Prognosis in AdultBCR-ABL1–Positive Acute Lymphoblastic Leukemia Patients

Iacobucci

Ferrari

Lonetti

et al. 2011

Clinical Cancer Research

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Purpose: The 9p21 locus, encoding three important tumor suppressors (p16/CDKN2A, p14/ARF, and p15/CDKN2B), is a major target of inactivation in the pathogenesis of many human tumors.Patients and Methods: To explore, at high resolution, the frequency and size of alterations affecting this locus in adult BCR-ABL1-positive acute lymphoblastic leukemia (ALL) and to investigate their prognostic value, 112 patients (101 de novo and 11 relapsed cases) were analyzed by genome-wide single-nucleotide polymorphism arrays and gene candidate deep exon sequencing. Paired diagnosis-relapse samples were further available and analyzed for 19 (19%) cases.Results: CDKN2A/ARF and CDKN2B genomic alterations were identified in 29% and 25% of newly diagnosed patients, respectively. Deletions were monoallelic in 72% of cases, and in 43% of them, the minimal overlapping region of the lost area spanned only the CDKN2A/B gene locus. An analysis conducted at relapse showed an increase in the detection rate of CDKN2A/ARF loss (47%) compared with the time of diagnosis (P ¼ 0.06). Point mutations within the 9p21 locus were found at very low levels, with only a nonsynonymous substitution in the exon 2 of CDKN2A. Of note, deletions of CDKN2A/B were significantly associated with poor outcomes in terms of overall survival (P ¼ 0.0206), disease free-survival (P ¼ 0.0010), and cumulative incidence of relapse (P ¼ 0.0014).Conclusions: Inactivation of the 9p21 locus by genomic deletion is a frequent event in BCR-ABL1-positive ALL. Deletions are frequently acquired during leukemia progression and are a poor prognostic marker of long-term outcomes. Clin Cancer Res; 17(23); 7413-23. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

CDKN2A/BAlterations Impair Prognosis in AdultBCR-ABL1–Positive Acute Lymphoblastic Leukemia Patients

Iacobucci

Ferrari

Lonetti

et al. 2011

Clinical Cancer Research

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“…The CDKN1A and CDKN2A genes encode functionally important cell cycle regulators; however, not much information on the variants in these genes is available vis-à-vis CRC risk. McCloud et al [2004] reported an association of the rs3088440:C4T polymorphism in the CDKN2A gene with a decreased risk of sporadic CRC and altered tumor progression. Two other studies did not report any association for polymorphisms in these cell cycle genes with colon cancer risk [Goodman et al, 2006] or CRC risk in the Israeli population [Starinsky et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have previously investigated the epigenetic changes in various genes including CDKN2A in neoplastic lesions in CRC patients [Miranda et al, 2006;Kawakami et al, 2006]. The role of polymorphisms in these genes for CRC susceptibility has not yet been fully investigated [McCloud et al, 2004].…”

Section: Introductionmentioning

confidence: 99%

Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic

et al. 2009

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The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population.

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“…Despite the demonstration of altered p16 protein function in conjunction with certain polymorphisms, no such association could be established for the other polymorphisms. Although the association between the altered protein function of p16 and progression of certain malignancies, including ovarian and upper gastrointestinal cancer (18)(19)(20), has been demonstrated, a similar correlation has not been established for pituitary adenomas and their progression.…”

Section: Introductionmentioning

confidence: 99%

Association between p16(CDKN2A) C540G polymorphism and tumor behavior in prolactinoma: A single-center study

et al. 2014

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Abstract. Pituitary tumors usually originate as benign sporadic adenomas and develop into invasive and aggressive tumors such as prolactinomas, which are common functioning pituitary adenomas. The aim of the present study was to examine the association between the tumor behavior in prolactinomas and the p16(CDKN2A) gene polymorphism occurring at the 3'-untranslated region of exon 3 (C540G). A total of 104 patients with prolactinoma were included and assigned to two groups based on invasive vs. non-invasive tumor behavior. Ki67 indices were recorded according to histopathology results. Genotypic analysis of the p16(CDKN2A) C540G polymorphism was carried out using a modified polymerase chain reaction-restriction fragment length polymorphism assay. The corresponding frequencies for CC, CG and GG genotypes in non-invasive vs. invasive tumors were 61.5, 30.8, 7.7 and 64.1, 28.2, 7.7%, respectively (not significant). The observed CG genotype frequency was higher compared with previous studies. In addition, the patients with giant adenomas or a high Ki67 index had a higher frequency of the CG genotype as compared with the other subgroups, although the differences were not significant (46.2 and 42.9%, respectively). In conclusion, a higher frequency of the C540G CG genotype of the CDKN2A gene was found among patients with prolactinoma in comparison with previous studies. These frequencies were also higher in the subgroups with elevated Ki67 or giant adenomas. Further studies are required to improve the definition of the role of the CG genotype in the development and progression of tumors in prolactinomas.

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p16INK4a polymorphism: associations with tumour progression in patients with sporadic colorectal cancer

Cited by 11 publications

References 0 publications

CDKN2A/BAlterations Impair Prognosis in AdultBCR-ABL1–Positive Acute Lymphoblastic Leukemia Patients

CDKN2A/BAlterations Impair Prognosis in AdultBCR-ABL1–Positive Acute Lymphoblastic Leukemia Patients

Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic

Association between p16(CDKN2A) C540G polymorphism and tumor behavior in prolactinoma: A single-center study

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