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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Genomic alterations in neuroendocrine cancers of the ovary
George Yaghmour1,2, Philippe Prouet3, Eric Wiedower1,2
1The West Cancer Center, 1588 Union Ave., Memphis, TN, 38104, USA.
Background:
As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO.
Methods:
Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007-2015 were identified. Tumors were assessed with up to 21 IHC stains, in situ hybridization of cMET, EGFR, HER2 and PIK3CA, and next-generation sequencing (NGS) as well as Sanger sequencing of selected genes.
Results:
Forty-six patients with SCCO (10 SCCO, 18 SCCO-HT, 18 NET-O) were identified as well as 58 patients with SCLC for comparison. Patients with SCCO and SCCO-HT were younger (median 42 years [range 12-75] and 26 years [range 8-40], respectively) than patients with NET-O 62 [range 13-76] or SCLC 66 [range 36-86]. SCCO patients were more likely to be metastatic (70 %) than SCCO-HT (50 %) or NET-O (33 %) patients, but at a similar rate to SCLC patients (65 %). PD1 expression varied across tumor type with SCCO (100 %), SCCO-HT (60 %), NET-O (33 %) vs SCLC (42 %). PDL1 expression also varied with SCCO (50 %), SCCO-HT (20 %), NET-O (33 %) and SCLC (0 %). No amplifications were identified in cMET, EGFR, or HER2 and only 1 was found in PIK3CA (NET-O). Actionable mutations were rare with 1 patient with SCCO having a BRCA2 mutation and 1 patient with NET-O having a PIK3CA mutation. No other actionable mutations were identified.
Conclusions:
No recurrent actionable mutations or rearrangements were identified using this platform in SCCO. IHC patterns may help guide the use of chemotherapy in these rare tumors.
Insights
Genomic profiling of small cell carcinoma of the ovary (SCCO) revealed no recurrent actionable mutations. Immunohistochemistry patterns may guide chemotherapy choices for this rare ovarian cancer.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Small cell carcinoma of the ovary (SCCO) is a rare and aggressive ovarian cancer with poor prognosis.
- Novel therapeutic strategies are needed for SCCO patients.
Purpose of the Study:
- To investigate the genomic landscape of SCCO using comprehensive profiling.
- To identify potential novel therapeutic targets for SCCO.
Main Methods:
- Genomic profiling including IHC, FISH, and NGS was performed on SCCO, SCCO-hypercalcemic type (SCCO-HT), neuroendocrine tumors of the ovary (NET-O), and small cell lung carcinoma (SCLC) samples.
- Analysis included up to 21 IHC stains and sequencing of key genes.
Main Results:
- No recurrent actionable mutations or rearrangements were identified in SCCO.
- PD1 and PDL1 expression varied across tumor types.
- One patient with SCCO had a BRCA2 mutation, and one with NET-O had a PIK3CA mutation.
Conclusions:
- Comprehensive genomic profiling did not reveal actionable targets in SCCO.
- Immunohistochemistry (IHC) patterns may inform chemotherapy selection for rare ovarian tumors like SCCO.
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