Anti-CDKN1B monoclonal antibody, clone JNE-38

Background: The '3PAs' syndrome, associating pituitary adenoma (PA) and pheochromocytoma/paraganglioma (PPGL), is sometimes associated with mutations in PPGL-predisposing genes, such as SDHx or MAX. In '3PAs' syndrome, PAs can occur before PPGL, suggesting a new gateway into SDHx/MAX-related diseases. Objective: To determine the SDHx/MAX mutation prevalence in patients with isolated PAs and characterize PAs of patients with SDHx/MAX mutations. Design: Genes involved in PAs (AIP/MEN1/CDKN1B) or PPGLs (SDHx/MAX) were sequenced in patients with isolated PAs. We then conducted a review of cases of PA in the setting of '3PAs' syndrome. Results: A total of 263 patients were recruited. Seven (likely) pathogenic variants were found in AlP, two in MEN1, two in SDHA, and one in SDHC. The prevalence of SDHx mutations reached 1.1% (3/263). Of 31 reported patients with PAs harboring SDHx/MAX mutations (28 published cases and 3 cases reported here), 6/31 (19%) developed PA before PPGL and 8/31 (26%) had isolated PA. The age of onset was later than in patients with AIP/MEN1 mutations. PAs were mainly macroprolactinomas and showed intracytoplasmic vacuoles seen on histopathology. Conclusions: We discovered SDHx mutations in patients bearing PA who had no familial or personal history of PPGL. However, the question of incidental association remains unresolved and data to determine the benefit of SDHx/MAX screening in these patients are lacking. We recommend that patients with isolated PA should be carefully examined for a family history of PPGLs. A family history of PPGL, as well as the presence of intracytoplasmic vacuoles in PA, requires SDHx/MAX genetic testing of patients.

Background: One of the most important factors leading to tumorigenesis is abnormality in the cells proliferation, because of the irregularity in cell cycle progression. CDKN2A (p16) and CDKN1B (p27) are tumor suppressors and regulators of cell cycle at G1 and G1-S transition. Any disorders in activity or expression of these two tumor suppressors can cause cancer. Aims: In this study, we appraised the relationship between 3 polymorphisms: p27 109VG (rs2066827) in exon1 and p16 [540CG (rs11515), 580CT (rs3088440)] in 3'UTR with the risk of colorectal cancer susceptibility in Iranian population. Subjects and methods: This case-control study was carried out on 214 cases with CRC and 233 control subjects. For p27 109VG and p16 (540CG, 580CT) genotyping, PCR-RFLP technique was used. Results: Logistic regression analysis revealed that G allele of p16 540CG significantly decreased the risk of CRC (OR = 0.63, CI = 0.42- 0.95, P = 0.031), but subjects with TT genotype of 580CT are more likely to develop CRC (OR = 4.63, CI = 1.28-16.71, P = 0.019). There were no significant relationships with p27 109VG and haplotype of p16 (540CG, 580CT) with CRC risk in Iranian population. However, coincidence in VG genotype of p27 109VG and CC genotype of p16 540CG has significantly increased the susceptibility to colorectal cancer (OR = 2.02, CI = 1.02-3.98, P = 0.042). Conclusion: This study indicates that the p16 [540CG (rs11515), 580CT (rs3088440)] polymorphisms are associated with the risk of CRC in Iranian population.