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- Targeted next-generation sequencing–based mutational signature analysis in endometrial cancer: utility and limitations across molecular subtypes
- Uijin Kim, Ahwon Lee, Keun Ho Lee, Sung Jong Lee, Sook Hee Hong, Donghyuk Lee, Jun Kang, Miseon Lee
- Received July 29, 2026 Accepted September 7, 2026 Published online November 10, 2026
- DOI: https://doi.org/10.4132/jptm.2026.09.07 [Epub ahead of print]
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Abstract
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Supplementary Material - Background
Molecular subtype classification is essential for staging endometrial cancer, planning adjuvant treatments, and stratifying prognosis. However, the correlation between mutational signature analysis using tumor-only targeted next-generation sequencing (NGS) data and molecular subtypes, as well as the interpretive value at the individual case level, remains inadequately characterized. Methods: We performed mutational signature analysis on tumor-only targeted NGS data from 72 endometrial cancer cases using the SATS R package. Molecular classification into four subtypes (POLE-mutated, mismatch repair deficient [MMRd], TP53-mutant, and no specific molecular profile [NSMP]) was established through a standard stepwise algorithm that integrated NGS and immunohistochemistry. Results: Out of the 72 endometrial cancers, 12 were classified as POLE-mutated, 10 as MMRd, six as TP53-mutant, and 44 as NSMP. All POLE-mutated tumors exhibited POLE-associated signatures (SBS10a/SBS10b), including cases with non-hotspot POLE exonuclease variants and tumor mutation burdens below the conventional ultramutation threshold. MMRd-associated signatures showed a broader distribution across molecular subtypes; while the summed MMRd-associated signatures were typically higher in MMRd tumors, low-level contributions were also noted in subsets of NSMP and TP53-mutant tumors. Within the POLE-mutated group, MMRd-associated signatures were more pronounced in cases displaying subclonal MMR protein loss as determined by immunohistochemistry. Conclusions: In this small, clinically selected cohort, targeted NGS-based mutational signatures provided exploratory, complementary information regarding POLE-associated mutagenesis and mixed MMR-related patterns. Overlapping signature distributions, dependence on the analytical pipeline, and the use of tumor-only targeted sequencing limit case-level interpretation. Mutational signature analysis should be interpreted in conjunction with established molecular tests and should not be used as a stand-alone classifier.
- Correlations between the Expression of c-Abl, c-Kit, Platelet-derived Growth Factor Receptor (PDGFR)-alpha and PDGFR-beta and Survival in Patients with Ovarian Cancer.
- Heejeong Lee, Keun Ho Lee, Kyo young Lee, Chang Suk Kang
- Korean J Pathol. 2006;40(3):210-216.
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- BACKGROUND
:Protein tyrosine kinases (PTKs) such as c-Abl, c-KIT, PDGFR-alpha and PDGFR-bata are key proteins in the regulation of cell growth. In this study, we evaluated the correlations between the expression of c-Abl, c-KIT, PDGFR-alpha and PDGFR-beta and the survival of patients with ovarian cancer.
METHODS
We performed the immunohistochemistry for 102 patients with ovarian cancer and we retrospectively reviewed the overall and disease free survival and also the response to platinum-based chemotherapy in those patients.
RESULTS
The short disease free survival rate was significantly associated with the increased expression of PDGFR-alpha (p=0.0459). The short overall survival time in patients with advanced (stage III and IV) ovarian cancer was associated with the overexpression of c-Abl (p=0.0268) and the reduced expression of c-KIT (p=0.0307). On multivariate analysis, the tumor stage and c-Abl maintained their prognostic influence. Meanwhile, none of the four PTK expression patterns predicted the response to the platinum-based chemotherapy.
CONCLUSIONS
Our data suggest that for patients with advanced ovarian cancer, the overexpression of c-Abl and the reduced expression of c-KIT might be used as poor prognostic factors for overall survival. It is further noteworthy that the tumor stage and c-Abl may be useful in predicting the patients' survival. Although any of the four PTKs could not predict the response to platinum chemotherapy, the expression of the kinases targeted by tyrosine kinase inhibitor suggests the potential usefulness of imatinib mesylate for the treatment of ovarian cancer.
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