TY - JOUR
T1 - KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size
AU - Corless, Christopher L.
AU - McGreevey, Laura
AU - Haley, Andrea
AU - Town, Ajia
AU - Heinrich, Michael C.
N1 - Funding Information:
Supported in part by grants from the Veteran’s Administration Merit Review Program, the Northwest Health Foundation (to M. C. H.), and the Oregon Cancer Institute (to C. L. C.).
PY - 2002
Y1 - 2002
N2 - Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gut wall that express the receptor tyrosine kinase KIT. Somatic mutations that result in constitutive activation of KIT kinase have been identified in a number of studies of GISTs, although the reported frequency of these mutations has varied over a wide range (20 to 92%). Several reports have suggested that KIT gene mutations are more common in malignant GISTs than in benign lesions, and it has been proposed that mutations in exon 11 of KIT are a negative prognostic factor. To maximize sensitivity for KIT mutations we have adapted denaturing high-pressure liquid chromatography as a method for screening polymerase chain reaction amplimers of exons 9, 11, 13, and 17 from GIST genomic DNA. This approach was used to assess the frequency of KIT mutations in 13 morphologically benign, incidentally discovered, GISTs identified at autopsy, endoscopy, or laparotomy for unrelated disease. Representing the smallest pathologically recognizable GISTs, these lesions ranged in size from 4 to 10 mm in diameter and were all immunohistochemically positive for KIT. Eleven of the 13 tumors had sequence-confirmed mutations in KIT, including 10 mutations in exon 11 (77%) and one mutation in exon 9 (7.7%). The remaining two tumors were wild type for exons 9, 11, and 17; one of these was also analyzed for exon 13 and was wild type in this exon as well. The mutations found in the incidental GISTs were identical to those that have been documented in larger GISTs. In addition, the overall frequency of mutations in the incidental tumors (85%) did not differ significantly from that we previously reported in a series of 72 advanced/metastatic GISTs (86%), strongly supporting the view that activating mutations in KIT are acquired very early in the development of most GISTs. The findings suggest that KIT mutations per se are of little prognostic importance in GISTs.
AB - Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gut wall that express the receptor tyrosine kinase KIT. Somatic mutations that result in constitutive activation of KIT kinase have been identified in a number of studies of GISTs, although the reported frequency of these mutations has varied over a wide range (20 to 92%). Several reports have suggested that KIT gene mutations are more common in malignant GISTs than in benign lesions, and it has been proposed that mutations in exon 11 of KIT are a negative prognostic factor. To maximize sensitivity for KIT mutations we have adapted denaturing high-pressure liquid chromatography as a method for screening polymerase chain reaction amplimers of exons 9, 11, 13, and 17 from GIST genomic DNA. This approach was used to assess the frequency of KIT mutations in 13 morphologically benign, incidentally discovered, GISTs identified at autopsy, endoscopy, or laparotomy for unrelated disease. Representing the smallest pathologically recognizable GISTs, these lesions ranged in size from 4 to 10 mm in diameter and were all immunohistochemically positive for KIT. Eleven of the 13 tumors had sequence-confirmed mutations in KIT, including 10 mutations in exon 11 (77%) and one mutation in exon 9 (7.7%). The remaining two tumors were wild type for exons 9, 11, and 17; one of these was also analyzed for exon 13 and was wild type in this exon as well. The mutations found in the incidental GISTs were identical to those that have been documented in larger GISTs. In addition, the overall frequency of mutations in the incidental tumors (85%) did not differ significantly from that we previously reported in a series of 72 advanced/metastatic GISTs (86%), strongly supporting the view that activating mutations in KIT are acquired very early in the development of most GISTs. The findings suggest that KIT mutations per se are of little prognostic importance in GISTs.
UR - http://www.scopus.com/inward/record.url?scp=0036092268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036092268&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)61103-0
DO - 10.1016/S0002-9440(10)61103-0
M3 - Article
C2 - 12000708
AN - SCOPUS:0036092268
SN - 0002-9440
VL - 160
SP - 1567
EP - 1572
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -