Details

Autor(en) / Beteiligte

• Walavalkar, Kaivalya
• Saravanan, Bharath
• Singh, Anurag Kumar
• Jayani, Ranveer Singh
• Nair, Ashwin
• Farooq, Umer
• Islam, Zubairul
• Soota, Deepanshu
• Mann, Rajat
• Shivaprasad, Padubidri V
• Freedman, Matthew L
• Sabarinathan, Radhakrishnan
• Haiman, Christopher A
• Notani, Dimple

Titel

A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer

Ist Teil von

• Nature communications, 2020-07, Vol.11 (1), p.3598-14, Article 3598

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Genetic variation at the 8q24 locus is linked with the greater susceptibility to prostate cancer in men of African ancestry. One such African ancestry specific rare variant, rs72725854 (A>G/T) (~6% allele frequency) has been associated with a ~2-fold increase in prostate cancer risk. However, the functional relevance of this variant is unknown. Here we show that the variant rs72725854 is present in a prostate cancer-specific enhancer at 8q24 locus. Chromatin-conformation capture and dCas9 mediated enhancer blocking establish a direct regulatory link between this enhancer and lncRNAs PCAT1, PRNCR1 and PVT1. The risk allele ('T') is associated with higher expression of PCAT1, PVT1 and c-myc in prostate tumors. Further, enhancer with the risk allele gains response to androgen stimulation by recruiting the transcription factor SPDEF whereas, non-risk alleles remain non-responsive. Elevated expression of these lncRNAs and c-myc in risk allele carriers may explain their greater susceptibility to prostate cancer.