For instance, as early as 2012, by investigating a plethora of lung cancer patient samples, Peifer and colleagues discovered that the genes CREBBP, EP300, and MLL, which are involved in the histone modification pathway, were mutated, thereby adversely affecting histone integrity, primarily in small-cell lung cancer (SCLC) with a poor prognosis. This evidence concerns the gene CREBBP and small cell lung carcinoma.