XAF-1 mutations linked to cancer susceptibility (SJ-15-0016)

St. Jude Reference #SJ-15-0016


Researchers at St. Jude developed a method for identifying individuals predisposed to cancer by detecting variants that lower the expression or inactivate the function of XAF-1 (X-linked inhibitor of apoptosis-associated factor 1). While studying patients with germline mutations in TP53, they noticed that patients who also harbored XAF-1 variants were more likely to develop different types of cancers and multiple tumors. XAF-1 genotyping is particularly important for carriers of germline TP53 variants, particularly the Brazilian population, in which both mutations often occur. Individuals with these mutations can benefit from close monitoring, genetic counseling and surveillance. These XAF-1 alterations can be easily detected by PCR-based assays, or adapted to include Sanger sequencing, TaqMan genotyping and SNP analysis, etc. We are seeking a partner to move this diagnostic assay forward toward commercialization. A patent application was filed and is available to interested parties under confidentiality.


More than 20 years ago, St. Jude researchers led by Raul Ribeiro, M.D., identified the TP53-R337H inherited variant among Brazilians. Pinto and her colleagues later identified TP53-R337H as a founder mutation, one introduced to Brazil during its colonization. While rare in the general population, TP53-R337H is common in Brazil. It is found in 1 out of every 300 Brazilians.

Using whole genome sequencing, the researchers identified a variant in the tumor suppressor gene XAF1 in a subset of TP53-R337H mutation carriers. Individuals who have inherited both the XAF1 variant and the TP53-R337H mutation are at a greater risk of cancer than those who have only the TP53-R337H mutation.

TP53 mutations are prevalent in individuals with rare pediatric adrenocortical carcinoma. However, TP53 mutations are a prominent factor in many other types of cancer. The knowledge that XAF1 modifies TP53 may fuel further research into whether this target can become the basis of novel treatment strategies.

Now that this (second) mutation is known, pharmaceutical companies can develop drugs to target the mutation, possibly correcting it. She expects genetic companies will also include the gene in their search forms. Please contact me for more information about licensing this technology as a diagnostic and/or drug development tool.


XAF-1, TP53 mutations, cancer, diagnostic, therapeutics, sarcoma, breast, adrenal, gastric, colon, lung, melanoma, neuroblastoma, epigenetic, assay, sequencing, genotyping and SNP analysis

Granted patents or published applications

Published as patent application WO 2019/202536 A1, but likely filing in Brazil only, due to presence of patient population.

Related scientific references

Science Advances  24 Jun 2020: Vol. 6, no. 26, eaba3231, DOI: 10.1126/sciadv.aba3231 https://advances.sciencemag.org/content/6/26/eaba3231

Inherited mutation found among Brazilians increases cancer risk

Licensing opportunities

We are seeking to patent a partner(s) to develop a diagnostic and therapeutics for these individuals and with which we can coordinate patenting.
Contact: chad.riggs@stjude.org.

Contact the Office of Technology Licensing (Phone: 901-595-2342, Fax: 901-595-3148) for more information.