We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer.
We report for the first time that ADP-ribosylation factor 1 (ARF1) is the most amplified gene in ARF gene family in breast cancer, and high-level amplification of ARF1 is associated with increased mRNA expression and poor outcomes of patients with breast cancer.
The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731).
In conclusion, Expression rates of p16 and pRB differ according to the molecular subgroups of breast cancer and they subsequently correlate with clnicopathologic factors.
In conclusion, DE-miRNAs in bladder cancer tissue samples and DE-targeted genes, such as miR-106b and CDKN2A, which were identified in the present study, may provide the basis for targeted therapy for breast cancer and enhance understanding of its pathogenesis.
Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-β (RARβ1) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin- fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100).
In a cross-sectional study of 138 women with no history of breast cancer who underwent reduction mammoplasty, we studied breast cancer risk factors, plasma and breast folate concentrations, variation in one-carbon metabolism genes, p16(INK4a) promoter methylation and P16 protein expression.
Melanoma-prone families with mutations in CDKN2A have an increased prevalence of a broad spectrum of cancers including lung, pancreatic, and breast cancer.
ASSET analyses identified four SNPs significantly associated with multiple cancers: rs3731239 (CDKN2A intronic) with ESCC, GC and BC (P = 3.96 × 10(-) (4)); rs10811474 (3' of IFNW1) with RCC and BrC (P = 0.001); rs12683422 (LINGO2 intronic) with RCC and BC (P = 5.93 × 10(-) (4)) and rs10511729 (3' of ELAVL2) with LC and BrC (P = 8.63 × 10(-) (4)).
CDK4 expression did not correlate with cyclin D1 expression or the survival data. p16 expression was associated with Human Epidermal Growth Factor Receptor 2 (HER2) negativity and increased breast cancer-specific survival and disease-free survival.
Three additional SNPs, including rs1011970 (9p21/CDKN2A/2B), rs941764 (14q32/CCDC88C), and rs17529111 (6q14/FAM46A), showed a significant association in analyses conducted by breast cancer subtype.
The present study concludes that hypermethylation of p14/ARF and p16/INK4a promoters demonstrate significant association with the risk of breast cancer, hence indicating these as important tumour suppressor genes involved in the pathogenesis of breast cancer in North Indian population (i.e.
p14 expression seems to increase initially in early breast cancer and decrease with further tumour progression. p14 may be induced to counteract immortalisation and hTERT surge.
In an effort to understand the molecular signature of BC in the Saudi population, we undertook this study to profile the methylation events in a series of key genes including Ras association (RalGDS/AF-6) domain family member 1 isoform a (RASSF1A), hypermethylated in cancer 1 (HIC1), cyclin-dependent kinase inhibitor 2A (CDKN2A), retinoic acid receptor beta (RARB2), estrogen receptor 1 (ESR1), progesterone receptor (PGR), paired-like homeodomain 2 (PITX2), secreted frizzled-related protein 1 (SFRP1), myogenic differentiation 1 (MYOD1), and slit homolog 2 (SLIT2), using MethyLight analysis in archival tumour samples.
On the other hand, cyclin B1, cdc2, p53 and p16 were overexpressed in breast cancer, showing correlation between the expression of cyclin B1 and cdc2 and breast cancers (p=0.00).
Promoter hypermethylation of PAX6, BRCA2, PAX5, WT1, CDH13 and MSH6 seems to be a frequent early event in breast cancer and methylation levels of GSTP1 (and CDKN2A, although still low) seem to increase with increasing DCIS grade.
PDCD2/4/6/8) and upregulation of some cell cycle regulatory genes (CDKN2A, CCNA2 etc.) was seen which may be in close relation to MDR in breast cancer.