Molecular subtypes of gastrointestinal stromal tumors and their prognostic and therapeutic implications.
Gastrointestinal stromal tumors (GISTs) are composed of various molecular subtypes, with differing prognostic and predictive relevance. Previously, tumors lacking mutations in the KIT and PDGFRA genes have been designated as 'wild-type' GISTs; however, they represent a heterogeneous group currently undergoing further subclassification. Primary and secondary resistance to imatinib poses a significant clinical challenge, therefore ongoing research is trying to evaluate mechanisms to overcome resistance. Thorough understanding of the prognostic and predictive relevance of different genetic subtypes of GIST can guide clinical decision-making both in the adjuvant and the metastatic setting. Further work is required to identify tailored therapies for specific subgroups of GISTs wild-type for KIT and PDGFRA mutations and to identify predictive factors of resistance to currently approved systemic therapies.
The Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
Zoltan
Z
Szucs
The Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
Khin
K
Thway
The Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
Cyril
C
Fisher
Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.
Ramesh
R
Bulusu
The Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
Anastasia
A
Constantinidou
The Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
Charlotte
C
Benson
The Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.|The Institute of Cancer Research, Cotswold Road, Sutton, SM2 5NG, UK.
Winette Ta
WT
van der Graaf
The Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
Robin L
RL
Jones
D000818:Animals; D014408:Biomarkers, Tumor; D000066491:Clinical Decision-Making; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D020440:Gene Duplication; D005838:Genotype; D006801:Humans; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit
BRAF; GIST; KIT; NF-1; PFGFRA; SDH deficiency; molecular subgroups; ‘wild-type’ GIST