MYC Amplification in Stomach and Gastroesophageal Junction Cancers: Clinical Associations

Overview

MYC gene amplification is frequently observed in gastric and gastroesophageal junction adenocarcinomas, with a higher prevalence in male patients. This amplification is associated with reduced efficacy of neoadjuvant FLOT chemotherapy, highlighting its potential role in tumor biology and treatment resistance.

Background

Gastric cancer (GC) is a common malignancy worldwide, with higher incidence rates in men and increasing cases in younger populations. Risk factors include Helicobacter pylori and Epstein-Barr virus infections, lifestyle factors, and genetic predispositions. Standard treatment for locally advanced GC involves perioperative FLOT chemotherapy, but intratumoral heterogeneity, including MYC gene amplification, complicates molecular characterization and targeted therapy. MYC, a transcription factor on chromosome 8q24, influences cancer hallmarks such as proliferation and apoptosis and is frequently amplified across multiple cancer types. Prior studies on MYC amplification in GC have been limited by small cohorts and lack of data on neoadjuvant treatment and gastroesophageal junction cancers.

Data Highlights

A total of 592 gastric and gastroesophageal junction adenocarcinoma samples from Caucasian patients were analyzed, divided into a chemotherapy naive cohort (470 patients) and a neoadjuvant FLOT-treated cohort (122 patients). MYC amplification was assessed using fluorescence in situ hybridization on whole mount tissue sections. Clinical parameters including sex, tumor stage, histology, and treatment response were collected and correlated with MYC status.

Key Findings

• MYC gene amplification was frequently detected in both stomach and gastroesophageal junction adenocarcinomas.
• Amplification was significantly associated with male gender, reflecting the higher incidence of GC in men.
• Neoadjuvant FLOT-treated patients with MYC amplification showed diminished tumor regression compared to non-amplified cases, indicating reduced chemotherapy efficacy.
• Intratumoral heterogeneity of MYC amplification was observed, complicating molecular characterization and potentially impacting treatment response.
• The study cohort consisted exclusively of Caucasian patients, providing relevant data for this population subgroup.

Clinical Implications

Assessment of MYC amplification status in gastric and gastroesophageal junction cancers may inform prognosis and predict response to neoadjuvant chemotherapy. Given its association with reduced efficacy of FLOT treatment, MYC amplification could serve as a biomarker to guide personalized therapeutic strategies. Awareness of intratumoral heterogeneity is important for accurate molecular diagnostics and treatment planning.

Conclusion

MYC gene amplification is a common molecular alteration in gastric and gastroesophageal junction adenocarcinomas, particularly in males, and is linked to poorer response to neoadjuvant chemotherapy. These findings underscore the biological and clinical significance of MYC in GC-GEJ and support further investigation into targeted approaches.

References

1. Cancer Statistics 2020 -- Incidence and Demographics
2. Becker et al. 2003 -- Tumor Regression Grading in Gastric Cancer
3. The Cancer Genome Atlas Research Network -- Molecular Subtypes of GC-GEJ
4. FLOT Chemotherapy Protocol -- Standard of Care in Locally Advanced GC