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
3330 - Tumour-infiltrating lymphocytes and BRCA-like status in stage III breast cancer patients treated with intensified carboplatin-based chemotherapy
Presenter: Leonora De Boo
Session: Poster Display session 2
Resources:
Abstract
3971 - Unravelling the biological characteristics of MammaPrint extreme risk subgroups
Presenter: Rajith Bhaskaran
Session: Poster Display session 2
Resources:
Abstract
5871 - Residual Cancer burden as a prognostic factor in a large series of Neoadjuvant chemotherapy. Subgroup analysis per molecular surrogated subtypes
Presenter: Catalina Falo
Session: Poster Display session 2
Resources:
Abstract
5014 - Clinical validation of CanAssist Breast in a Spanish cohort
Presenter: Manjiri Bakre
Session: Poster Display session 2
Resources:
Abstract
2787 - Meta-analysis on association of pathological complete response with long-term survival outcomes in triple-negative breast cancer
Presenter: Peter A. Fasching
Session: Poster Display session 2
Resources:
Abstract
4301 - Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial
Presenter: Gaia Griguolo
Session: Poster Display session 2
Resources:
Abstract
3205 - Frequency of germline mutations in women's cancer susceptibility genes in a large cohort of Chinese breast cancer patients
Presenter: Ning Liao
Session: Poster Display session 2
Resources:
Abstract
4091 - Triple blinded Prospective Study assessing the Impact of Genomics & Artificial Intelligence Watson For Oncology (WFO) on MDT’s Decision of Adjuvant Systemic Therapy for Hormone Receptor Positive Early Breast Carcinoma-
Presenter: Somashekhar Sampige Prasannakumar
Session: Poster Display session 2
Resources:
Abstract
4359 - Prognostic significance of Progesterone Receptor levels in luminal-like Her2- early Breast Cancer patients. A retrospective single Cancer Center analysis.
Presenter: Anna Diana
Session: Poster Display session 2
Resources:
Abstract
1369 - PAM50 HER2-enriched subtype and pathological complete response in HER2-positive early breast cancer: a meta-analysis
Presenter: Francesco Schettini
Session: Poster Display session 2
Resources:
Abstract