Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells

摘要: Genetic mutations are known to drive cancer progression and certain tumors have mutation signatures that reflect exposures environmental carcinogens. Benzo[a]pyrene (BaP) has a signature proven capable of inducing changes DNA sequence drives normal pre-stasis human mammary epithelial cells (HMEC) past first tumor suppressor barrier (stasis) toward immortality. We analyzed normal, HMEC, three independent BaP-derived post-stasis HMEC strains (184Aa, 184Be, 184Ce) two their immortal derivatives(184A1 184BE1) by whole exome sequencing. The exhibited between 93 233 BaP-induced in exons. Seventy percent the were C:G>A:T transversions, consistent with spectrum BaP. Mutations predicted impact protein function occurred several putative drivers including p16, PLCG1, MED12, TAF1 184Aa; PIK3CG, HSP90AB1, WHSC1L1, LCP1 184Be FANCA, LPP 184Ce. Biological processes typically harbor driver such as cell cycle, regulation death proliferation, RNA processing, chromatin modification repair found each strains. Spontaneously immortalized lines derived from shared greater than 95% precursor cells. These had 10 or fewer additional point relative precursors, but acquired chromosomal anomalies during immortalization arose results this study indicate acute high dose BaP recapitulate patterns can induce number genes.