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Study Probes Genetic Role in Papillary Thyroid Cancer

In adult stomic-bomb survivors, RET/PTC rearrangements appear to contribute to cancer

WEDNESDAY, Sept. 3 (HealthDay News) -- In survivors of the Nagasaki and Hiroshima atomic bombings, rearrangements of RET/PTC, rather than BRAFV600E mutation, appear to be closely linked to radiation-associated adult-onset papillary thyroid cancer (PTC), according to research published in the Sept. 1 issue of Cancer Research.

Kiyohiro Hamatani, Ph.D., of the Radiation Effects Research Foundation in Hiroshima, Japan, and colleagues analyzed tumor specimens from 71 atomic-bomb survivors with adult-onset PTC for RET/PTC rearrangements and BRAFV600E mutation. The authors write that the former issue is a major event in childhood PTC -- regardless of radiation exposure -- and the latter is the most common molecular event in general adult-onset disease.

The researchers found that the frequency of RET/PTC rearrangements grew more common with increasing radiation dose, shorter elapsed time since radiation exposure, and younger age at the time of the bombing. However, BRAFV600E mutation fell in frequency with increased radiation dose. Individuals with the disease with RET/PTC rearrangements developed the cancer earlier than individuals with BRAFV600E mutation.

"In PTC, the RET proto-oncogene is activated by fusion of the RET TK domain with the 5' terminal sequence of one of different heterologous genes via rearrangements that generate a series of chimeric-transforming oncogenes collectively described as RET/PTCs," the authors write. "The BRAF gene encodes a serine/threonine kinase responsible for transduction of signals in the MAP-kinase cascade. BRAF somatic mutations were first discovered in several types of human cancers, including malignant melanomas."

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