Somatic mutations have been related to the highest incidence of metastatic disease and different treatment responses. The molecular cause of prostate cancer (PC) is still unclear; however, its progression involves alterations in oncogenes and tumor suppressor genes as well as somatic mutations such as the ones in PIK3CA gene.
A high percentage of PC is considered sporadic, which means that the damage to the genes occurs by chance after birth (mainly somatic mutations will drive the cancer event). However, little is known about somatic mutations in PC development.
We evaluated prostate biopsies in the main somatic mutations genes (PIK3CA, TP53, EGFR, KIT, KRAS, PTEN, and BRAF) among individuals with PSA values>4ng/ml (n = 125), including affected and unaffected PC subjects.
Mutations in KIT gene are related to aggressive PC: TNM stages II to III, Gleason score ≥ 7 and D'Amico risk (P = 0.037, 0.040, and 0.017). However, there are no statistical significant results when more than 3 somatic mutations are presented in the same individual. In relation to environmental factors (smoking, diet, alcohol intake, or workplace exposure) there are no significant differences in the effect of environmental exposure and the somatic mutation presence. The most prevalent mutations among patients with PC are c.1621A>C (rs3822214) in KIT, c.38G>C (rs112445441) in KRAS and c.733G>A (rs28934575) in TP53 genes. KRAS, KIT, and TP53 genes are the most prevalent ones in patients with PC.
Somatic alterations predisposing to chromosomal rearrangements in PC remain largely undefined. We show that KIT, KRAS, and TP53 genes have a higher presence among patients with PC and that mutations in KIT gene are related to an aggressive PC. However, we did not find any environmental effect in somatic mutations among PC individuals.
Urologic oncology. 2018 Apr 09 [Epub ahead of print]
Luis Javier Martinez-Gonzalez, Manrique Pascual Geler, Inmaculada Robles Fernandez, Jose Manuel Cozar, Jose Antonio Lorente, Maria Jesus Alvarez Cubero
GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Av. Ilustracion, 114 - PTS - 18016 Granada, Spain. Electronic address: ., Urology Department, University Hospital Virgen de las Nieves, Granada, Spain., GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Av. Ilustracion, 114 - PTS - 18016 Granada, Spain., GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Av. Ilustracion, 114 - PTS - 18016 Granada, Spain; University of Granada, Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine -PTS, 18016 Granada, Spain., GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Av. Ilustracion, 114 - PTS - 18016 Granada, Spain; University of Granada, Department of Biochemistry & Molecular Biology III - Faculty of Medicine - PTS, 18016 Granada, Spain. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/29650325
Go Beyond the Abstract and Read a Commentary by the Author: Maria Jesús Alvarez Cubero, MD, Ph.D.