C88
KIT and PDGFRα mutations are present in over 80% of very low risk gastrointestinal stromal tumours: analysis of 18 gastrointestinal stromal tumours under 2cm in size
Brendan O'Sullivan1, Graham Caine1, Nayneeta Deshmukh1, Rahul Hedjmadi1, Gary Reynolds2, Olga Tucker1, Ian Geh1, Philippe Taniere1
1UHB NHS Foundation Trust, Birmingham, West Midlands, UK, 2University of Birmingham, Birmingham, West Midlands, UK
Background
We present data on a series of 18 very low risk Gastrointestinal Stromal Tumours (GIST), illustrating that the classical mutations in KIT and PDGFRα genes which are commonplace in larger, clinically presenting tumours are found with similar frequency and spectrum in the very low risk “tumourlets”.
Method
Samples were obtained as incidental findings in resection specimens from non-GIST primary tumours (15/18) or in association with other larger clinically presenting GIST (3/18). DNA was extracted from tissue sections, amplified by PCR, and screened for mutations in exons 9, 11, 13&17 of the KIT gene and exons 12, 14&18 of the PDGFRα gene (bi-directional sequencing, positive results confirmed by duplication).
Results
Size of GIST tumourlets was 2-17mm. Distribution by location was as follows: stomach, 11 cases; small intestine, 4 cases; rectum, omentum, peritoneum, 1 case each. Viable DNA was extracted from 16 of 18 tumours. Mutations were found in 13 of 16 cases screened (81%); 9 in KIT exon 11, and 1 each in KIT exons 9 and 17, and PDGFRα exons 12 and 18.
Conclusion
Rate and spectrum of mutation matches that in the general GIST population, and is notably higher than in many previous similar studies. This suggests a fundamental early developmental role for such mutations. Such cases require appropriate follow up and monitoring given the malignant potential and resistance to targeted therapies endowed by such mutations. However, it does not rule out a “second hit” as the trigger for growth and development to the stage of clinical presentation.
