Abstract 3901
Background
Biliary tract cancers (BTCs) are a group of relatively rare invasive carcinomas including gallbladder carcinoma (GBC), intrahepatic (ICC), hilar (HCCA) and extrahepatic (ECC) cholangiocarcinoma. Clinical trials of PI3K/AKT/mTOR inhibitors have revealed PI3K and PTEN mutations as effective biomarkers. This study aimed to analyze the gene mutations involved in this pathway and other gene mutations in Chinese BTC patients and to analyze the profiling characteristics of each subtype.
Methods
A total of 661 (125 ECC, 159 GBC, 47 HCCA, and 330 ICC) BTC patients were included in this study. FFPE and matching blood samples from these patients were collected and sequenced using next-generation sequencing targeting 450 cancer genes. Genomic alterations including single nucleotide variants, insertions, and deletions, copy number variations and fusions were assessed.
Results
A total of 17.9% (118/661) of patients were identified harboring PI3K/AKT/mTOR pathway mutations. In preclinical data, RAS gene (KRAS/HRAS/NRAS) mutations might lead to reduced sensitivity to mTOR inhibitors. There was 11.8% (39/330) in ICC, 7.2% (9/125) in ECC, 12.8% (6/47) in HCCA and 25.2% (40/159) in GBC detected with PI3K pathway mutations and RAS wildtype, where the GBC proportion was statistically significantly higher than any other subtypes. A total of 3.6% (24/661) of patients presented co-occurrence of RAS and PI3K pathway mutations, but this was not found in HCCA. The percentages of co-occurrence in ICC, ECC and GBC were 3.6% (12/330), 4.0% (5/125) and 4.4% (7/159), respectively. The top 3 mutated genes in the PI3K/AKT/mTOR pathway were PIK3CA at 45.8% (54/118), PTEN at 22% (26/118) and TSC2 at 9.3% (11/118). PIK3CA mutations and amplification were discovered in 52 patients and 2 patients, respectively, including 23 ICC and 23 GBC patients, the most frequent being E542K (12/52) and52) mutations./52) mutations.
Conclusions
In Chinese BTC patients, the incidence (3.6%) of RAS and PI3K pathway mutation’s co-occurrence was generally low. Among BTC subtypes, GBC patients had the highest mutation proportion (25.2%) involved in the PI3K/AKT/mTOR pathway with wildtype RAS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Dan Liu.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5694 - Findings from a new specialist remote Counselling Service for Neuroendocrine Neoplasm (NEN) patients and family members
Presenter: Catherine Bouvier
Session: Poster Display session 2
Resources:
Abstract
4725 - Hematologic malignancies in temozolomide-treated metastatic pancreatic neuroendocrine tumors
Presenter: Nicole Balmaceda
Session: Poster Display session 2
Resources:
Abstract
5842 - Efficacy and toxicity of combination chemotherapy with cyclophosphamide, vincristine and an anthracycline in patients with metastatic extrapulmonary neuroendocrine carcinoma
Presenter: Leonidas Apostolidis
Session: Poster Display session 2
Resources:
Abstract
1543 - An Australian multi-centre experience of the use of peptide receptor radionuclide therapy for bronchial carcinoid tumours.
Presenter: Lisi Lim
Session: Poster Display session 2
Resources:
Abstract
4175 - Extra-pulmonary (EP) high grade (HG) neuroendocrine carcinoma (NEC): real-life outcomes of fifty-eight patients from a Portuguese cancer center.
Presenter: Rita Conde
Session: Poster Display session 2
Resources:
Abstract
3274 - Efficacy of immune check-point inhibitors (ICPi) in large cell neuroendocrine tumors of lung (LCNET)
Presenter: Shira Sherman
Session: Poster Display session 2
Resources:
Abstract
3534 - HORMONET: Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression
Presenter: Milton Barros
Session: Poster Display session 2
Resources:
Abstract
2137 - Clinical utility of Metabolic Tumor Volume in Papillary Thyroid Carcinoma
Presenter: Norihiko Takemoto
Session: Poster Display session 2
Resources:
Abstract
3864 - Correlation of thyroglobulin (Tg) oscillations with progression-free survival (PFS) in patients with radioactive iodine-refractory (RAI-R) differentiated thyroid carcinoma (DTC) treated with multikinase inhibitors (MKI).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract
2820 - Analytical validation of a thyroid cancer diagnostic method based on the relative quantification of CLDN10, HMGA2 and LAMB3 expression
Presenter: Mateus Barrosfilho
Session: Poster Display session 2
Resources:
Abstract