Winn/Miller Trust Grant report
MT12-009: Gene identification for mediastinal lymphoma in Oriental and Siamese type cats; $19,482.00, Dr. Leslie Lyons
Lymphosarcoma (LSA, lymphoma) is the most common cancer of cats worldwide. All breeds are susceptible, as are large felids such as the lion, tiger and cheetah. This cancer is also one of the most common cancers in dogs and people. Young cats of the Siamese and Oriental breeds are susceptible to a novel form of LSA; in these breeds, the cancer occurs early (generally when cats are young adults in the prime of their life), and the cancer is situated at the front of the chest (in the cranial mediastinum). LSA in this cohort of cats seems different to other forms of LSA in (i) being unassociated with retroviruses (FIV and FeLV), and (ii) having greater sensitivity to chemotherapy agents (which means many affected cats can be successfully treated using sequential multi-agent chemotherapy).
Previous studies funded by the Cat Health Network have helped localize a critical suspect gene to cat chromosome D1. A gene in this region is significantly suspected of being involved with the Oriental cat LSA. Critically, by determining the gene(s) responsible for this type of cancer in Siamese/Oriental cats, a PCR test to identify carriers can be developed, and thereby prevent the next generation of Siamese and Oriental shorthairs developing LSA. Cats used in this study might also prove useful in future studies of genetic conditions commonly seen in Siamese and Oriental cats, such as hepatic amyloidosis. This gene could then be analyzed in other cats with other forms of lymphosarcoma to determine if genetic markers can identify risk.
This study examined the genetic sequence of the prime candidate gene (called PTPRJ) for autosomal recessive mediastinal lymphoma in the Oriental cats. The regions of this gene that make the protein were DNA sequenced in cats that were normal and those that had the cancer. Although some variation was identified between cats, no DNA variation was suggested to cause a change in the protein or was concordant with cats that had disease. Therefore an alternative approach was initiated, which was to examine other candidate genes for causative variants. Candidate genes are in the process of being identified through sequencing of the entire genome (all chromosomes) of multiple cats. This project will provide large amounts of information that can be shared among researchers examining genetically inherited disease conditions. The analysis for mutations is ongoing; any variations found will be screened for in affected cats to hopefully identify any link to lymphoma.
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