Whilst changes in the composition and architecture are the major collagen alterations in lung tumors, mutations in collagen type V alpha 2 chain (COL5A2) and collagen type II alpha I chain (COL2A1) genes have also been detected in subclonal secondary lung tumors following genomic doubling events in both adenocarcinoma and squamous carcinoma (44). Here, COL5A2 is linked to squamous cell carcinoma.