|
|
|
|
|
|
|
|
Abstract
Highlights
- •
- Genotyping with SNaPshot identified few drugable targets in serous cancers.
- •
- SNaPshot may have merit in endometrial cancer where PI3kinase signaling is important.
- •
- Genotyping platforms should be chosen to reflect disease and histology.
Abstract
Background
Genetic
abnormalities underlie the development and progression of cancer, and
represent potential opportunities for personalized cancer therapy in Gyn
malignancies.
Methods
We
identified Gyn oncology patients at the MGH Cancer Center with tumors
genotyped for a panel of mutations by SNaPshot, a CLIA approved assay,
validated in lung cancer, that uses SNP genotyping in degraded DNA from
FFPE tissue to identify 160 described mutations across 15 cancer genes (AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, IDH1, KIT, KRAS, MAP2KI, NOTCH1, NRAS, PIK3CA, PTEN, TP53).
Results
Between
5/17/10 and 8/8/13, 249 pts consented to SNaPshot analysis. Median age
60 (29–84) yrs. Tumors were ovarian 123 (49%), uterine 74(30%), cervical
14(6%), fallopian 9(4%), primary peritoneal 13(5%), or rare 16(6%) with
the incidence of testing high grade serous ovarian cancer (HGSOC)
halving over time. SNaPshot was positive in 75 (30%), with 18 of these
(24%) having 2 or 3 (n = 5) mutations identified. TP53
mutations are most common in high-grade serous cancers yet a low
detection rate (17%) was likely related to the assay. However, 4 of the 7
purely endometrioid ovarian tumors (57%) harbored a p53 mutation. Of
the 38 endometrioid uterine tumors, 18 mutations (47%) in the PI3Kinase
pathway were identified. Only 9 of 122 purely serous (7%) tumors across
all tumor types harbored a ‘drugable’ mutation, compared with 20 of 45
(44%) of endometrioid tumors (p < 0.0001). 17 pts
subsequently enrolled on a clinical trial; all but 4 of whom had PIK3CA
pathway mutations. Eight of 14 (47%) cervical tumors harbored a
‘drugable’ mutation.
Conclusion
Although
SNaPshot can identify potentially important therapeutic targets, the
incidence of ‘drugable’ targets in ovarian cancer is low. In this
cohort, only 7% of subjects eventually were treated on a relevant
clinical trial. Geneotyping should be used judiciously and reflect
histologic subtype and available platform.
0 comments :
Post a Comment
Your comments?
Note: Only a member of this blog may post a comment.