Coupled with later findings that genetic alteration of the POLR3A locus was exclusively found in anti-RNAP III-positive SSc patients with cancer than without and that POLR3A mutation triggered cellular immunity and cross-reactive humoral immune responses [86], the current hypothesis is that malignancy may initiate the scleroderma-specific immune response and drive disease in a subset of scleroderma patients. Here, POLR3A is linked to scleroderma.