Biomedical Engineering Reference
In-Depth Information
adult counterparts in both clinical and molecular characteristics.
These tumors are preferentially diagnosed in females and occur
as multifocal neoplasms with epithelioid or mixed morphology
within the stomach. These tumors tend to recur and metastasize,
and metastatic sites may include lymph nodes in addition to sites
typically seen in older adults (such as liver and peritoneum) [77].
Despite this tendency, pediatric GISTs have favorable long-term
prognoses [77, 78]. The risk stratification system (Table 9.1) used
for adult GISTs is less predictive when applied to pediatric tumors
[78]. Young adult GIST patients are a mixed group, with some more
typical of pediatric GISTs and others more characteristic of GISTs in
older adults.
While KIT protein expression by immunohistochemistry is the
norm, the vast majority of these pediatric tumors are
KIT/PDGFRA
wild-type, with only rare mutant tumors being reported [78, 79].
Though lacking mutations in
, these tumors show
similar KIT activation (phosphorylation) levels to those found in
KIT/PDGFRA
KIT
mutant tumors and adult WT GISTs [25, 77]. In the small number of
pediatric GISTs tested, mutations of
have not been detected.
While late onset mutant GISTs progressing to malignancy
demonstrate several chromosomal alterations (such as losses of 9p
and 13p, gains in 5p, 8q, 17q and 20q), pediatric wild-type GISTs
do not exhibit large-scale chromosomal changes [19, 25] (Fig. 9.4).
Two gene expression profiling studies have shown that wild-type
pediatric and young adult GISTs cluster together and separate from
late onset GISTs (whether mutant or wild-type). Several differentially
regulated genes in the pediatric/young adult group were identified in
these studies but their only common finding was upregulation of IGF-
1R [77, 79]. Indeed IGF-1R protein and mRNA are more frequently
overexpressed in wild-type adult and pediatric GISTs in comparison
with mutant GISTs, raising the possibility of a therapeutic target in
this subset of tumors [75, 80]. Overall, the genetic changes in GISTs,
both adult and pediatric, without
BRAF
mutations is
not known, so we and others are currently using modern day deep
sequencing approaches to further explore the GIST genome in these
patients to uncover additional clues to help define therapy.
KIT/PDGFRA/BRAF
