Clinicians should consider genetic testing, including the entire CDKN2A locus, in their patients with LFS/ LFL or those with personal history of sarcoma, and family history of cancers beyond the traditional spectrum of CDKN2A. To the best of our knowledge, this is also the first report of a human p14ARF deficiency model, providing insights into the potential role of p14ARF and deregulation of the p53 pathway in sarcoma tumour development. Here, CDKN2A is linked to cancer.