NANETS2024 17th Annual Multidisciplinary NET Medical Symposium NANETS 2024 Applied Basic Science (13 abstracts)
Comparison of pulmonary versus extra-pulmonary small cell neuroendocrine carcinomas demonstrate distinct genomic alterations
A. Mohamed 1 , E. Teslow 2 , E. Jaeger 2 , M. Stoppler 2 , S.L Asa 3 , S.H. Tirumani 4 , L. Qiubai 4 , A. Mahipal 1 , D. Bajor 1 , S. Chakrabarti 1 , J.E. Selfridge 1 , M. Lumish 1 , M. Conces 1 , R.S. Hoehn 5 , J. Winter 5 , J. Ammori 5 , J. Hardacre 5 , L.E. Henke 6 & A Dowlati 1
1Department of Medicine, Division of Medical Oncology, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH; 2Tempus AI, Inc., Chicago, IL; 3Department of Pathology, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH; 4Department of Radiology, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH; 5Department of Surgical Oncology, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH; 6Department of Radiation Oncology, University Hospitals, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
Background: Small cell neuroendocrine carcinomas (SC-NECs) are uncommon but aggressive tumors with poor prognosis. Although both small cell lung cancer (SCLC) and extrapulmonary small cell NEC (EP-SC-NEC) have similar histological and morphological characteristics, whether they are biologically distinct is still unknown. We assessed and compared the genomic profiles of SCLC and EP-SC-NECs to identify distinct mutations that may allow for more personalized therapeutic options.
Methods: Patients with a histological diagnosis of SC-NEC were identified from the de-identified Tempus real-world multimodal database and stratified by primary tumor site and categorized as SCLC or EP-SC-NEC. Patient demographic/clinical characteristics and genomic/transcriptomic data were described as N (%) or median (IQR), min, and max and compared between groups by Chi-squared/Fisher’s Exact tests or Wilcoxon rank-sum tests, as applicable. The prevalence of somatic mutations (SNVs, CNVs, and Fusions) was compared similarly, with a false-discovery rate correction for multiple comparisons. Analyses were two-sided, with statistical significance evaluated at the 0.05 alpha level.
Results: 228 SCLC vs 186 EP-SC-NEC were compared. The two groups did not differ in age, race, or ethnicity when diagnosed. SCLC samples had significantly higher median TMB than EP-SC-NEC samples (5.0 vs 3.4 mut/MB, P < 0.001). MSI-H was rare in both groups (SCLC 0.4% vs EP-SC-NEC 2.7%, P = 0.10). There were significant differences in SNVs with TP53, RB1, EGFR, and NOTCH1 mutations more common and TERT, ARID1A, APC, FOXA1, and CTNNB1 mutations less common in SCLC (q<0.05). SCLC also had significantly fewer CCNE1 amplifications than EP-SC-NEC. Pathogenic fusions were also more frequent in EP-SC-NEC vs SCLC (q<0.001), with 24% of EP-SC-NEC fusions being TMPRSS2-ERG.
Conclusions: Despite the histological and morphological overlap between SCLC and EP-SC-NECs, our data revealed heterogeneous molecular characteristics between both groups. These distinct molecular signatures could impact therapeutic decisions for SC-NEC according to their site of origin.
ABSTRACT ID28477
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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