12q21.2

DT1P1B11,PHRIP,TDAG51

Melanoma

PHLDA1 expression was associated with reduced cell growth and colony formation and with increased apoptotic rates and drug sensitivity in melanoma cell lines. Loss of PHLDA1 has been correlated with melanoma progression (Neef et al., 2002).

Breast cancer

Down-regulation of PHLDA1 mRNA and protein expression is frequently observed in primary invasive breast tumours. Down-regulation of PHLDA1 protein has been shown to be a strong predictor of poor prognosis for breast cancer patients, indicating that reduced PHLDA1 expression contribute for breast cancer progression and might serve as useful prognostic biomarker of disease outcome (Nagai et al., 2007).

Oral cancer

Reduced expression of PHLDA1 was observed in 60,7% of oral squamous cell carcinomas (OSCC), especially in well-differentiated tumors. Positive PHLDA1 immunostaining was associated with advanced clinical stages of the disease, suggesting that PHLDA1 has a functional role in oral tumorigenesis. Overall and disease-free survival rates were significantly better in patients with tumors that were negative for PHLDA1, and a multivariate analysis suggested that PHLDA1 is an independent prognostic factor in OSCC patients (Coutinho-Camillo et al., 2013).

Colon cancer

Altered PHLDA1 expression has been shown to be associated with the process of intestinal tumorigenesis (Sakthianandeswaren et al., 2011).

Basal cell carcinoma

PHLDA1 has also been shown to be a follicular and epithelial stem cell marker (Ohyama et al., 2006; Sakthianandeswaren et al., 2011) with potential to differentiates between trichoepithelioma and basal cell carcinoma (Sellheyer and Nelson, 2011).

Atherosclerosis

In vivo and in vitro studies demonstrated that increased PHLDA1 expression induced by homocysteine promotes detachment-mediated programmed cell death and contributes to the development of atherosclerosis (Hossain et al., 2003). Genetic variant in an intergenic region of the PHLDA1 gene (rs2367446) has been shown to be associated with the development of cardiovascular diseases (Hossain et al., 2013).

Epilepsy

PHLDA1 expression has been shown to be higher in the anterior temporal neocortex from patients with intractable epilepsy when compared with the levels observed in the neocortex from the control group, suggesting a possible association of PHLDA1 in the physiopathology of the disease (Xi et al., 2007).