title: Genomic alterations in neuroendocrine cancers of the ovary.
abstract: 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.
authors: The West Cancer Center, 1588 Union Ave., Memphis, TN, 38104, USA.|Department of Hematology & Oncology, The University of Tennessee Health Science Center, 956 Court Ave., Suite H310A, Memphis, TN, 38163, USA.
authors: George
authors: G
authors: Yaghmour
authors: Department of Internal Medicine, The University of Tennessee Health Science Center, 956 Court Ave., Suite H314, Memphis, TN, 38163, USA. pprouet@uthsc.edu.
authors: Philippe
authors: P
authors: Prouet
authors: The West Cancer Center, 1588 Union Ave., Memphis, TN, 38104, USA.|Department of Hematology & Oncology, The University of Tennessee Health Science Center, 956 Court Ave., Suite H310A, Memphis, TN, 38163, USA.
authors: Eric
authors: E
authors: Wiedower
authors: Department of Internal Medicine, The University of Tennessee Health Science Center, 956 Court Ave., Suite H314, Memphis, TN, 38163, USA.
authors: Omer Hassan
authors: OH
authors: Jamy
authors: Caris Life Sciences, 4750 S. 44th Place, Phoenix, AZ, 85040, USA.
authors: Rebecca
authors: R
authors: Feldman
authors: The West Cancer Center, 1588 Union Ave., Memphis, TN, 38104, USA.|Department of Hematology & Oncology, The University of Tennessee Health Science Center, 956 Court Ave., Suite H310A, Memphis, TN, 38163, USA.
authors: Jason C
authors: JC
authors: Chandler
authors: The West Cancer Center, 1588 Union Ave., Memphis, TN, 38104, USA.|Department of Hematology & Oncology, The University of Tennessee Health Science Center, 956 Court Ave., Suite H310A, Memphis, TN, 38163, USA.
authors: Manjari
authors: M
authors: Pandey
authors: The West Cancer Center, 1588 Union Ave., Memphis, TN, 38104, USA.|Department of Hematology & Oncology, The University of Tennessee Health Science Center, 956 Court Ave., Suite H310A, Memphis, TN, 38163, USA.
authors: Mike G
authors: MG
authors: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D002648:Child; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010053:Ovary / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: Actionable mutation; Chemotherapy; Genomic profiling; Gynecologic malignancies; Small cell carcinoma of ovary