Within NSCLC specifically, FISH assays identified the primary region of 4q21.2-22.1 to be associated with poor prognosis [44, 46, 47], and a recent study from this same group showed that hypermethylation of HERC5 promoter (located at 4q22.1), and thus under-expression of the gene correlated with: positive disseminated tumor cells in the bone marrow, brain metastasis, and poor survival in both stage I adenocarcinoma and metastatic lung cancer patients [46]. Here, HERC5 is linked to adenocarcinoma.