Esophageal Cancer: Genomic and Molecular Characterization, Stem Cell Compartment and Clonal Evolution

Abstract

Esophageal cancer (EC) is the eighth most common cancer and is the sixth leading cause of death worldwide. The incidence of histologic subtypes of EC, esophageal adenocarcinoma (EAC) and esophageal squamous carcinoma (ESCC), display considerable geographic variation. EAC arises from metaplastic Barrett’s esophagus (BE) in the context of chronic inflammation secondary to exposure to acid and bile. The main risk factors for developing ESCC are cigarette smoking and alcohol consumption. The main somatic genetic abnormalities showed a different genetic landscape in EAC compared to ESCC. EAC is a heterogeneous cancer dominated by copy number alterations, a high mutational burden, co-amplification of receptor tyrosine kinase, frequent TP53 mutations. The cellular origins of BE and EAC are still not understood: animal models supported a cellular origin either from stem cells located in the basal layer of esophageal epithelium or from progenitors present in the cardia region. Many studies support the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. The exact identification of these CSCs, as well as their role in the pathogenesis of EAC and ESCC remain still to be demonstrated. The reviewed studies suggest that current molecular and cellular characterization of EAC and ESCC should serve as background for development of new treatment strategies.

The Use of Circulating Tumor DNA for Prognosis of Gastrointestinal Cancers

“…Most gastrointestinal cancers are thought to develop through a series of epigenetic changes or somatic (non-hereditary) lesions. The common mutations are in genes including APC, TP53, KRAS and BRAF for colorectal cancer [reviewed in Testa et al ( 40 )], TP53 and p16/CDKN2A in oesophageal adenocarcinomas [reviewed in Testa et al ( 41 )] , CDH1, PIK3CA , and RHOA in gastric cancers [reviewed in Ang et al ( 42 )], and KIT and PDGFRA with GIST [reviewed in Wozniak et al ( 43 )]. These alterations can contribute to aberrant cell behavior such as uncontrolled cell growth and proliferation, disordered apoptosis, increased angiogenesis, and promotion of invasion and metastasis ( 44 ).…”

Molecular landscape of esophageal cancer: implications for early detection and personalized therapy

“…19,20 Although TP53 is the most commonly altered gene in both EAC and ESCC (with alterations observed in > 80% of all samples analyzed), there is consensus that the profile of genomic alterations in EAC and ESCC vary considerably. 21 In EAC, the genes that are altered more frequently than in ESCC include ERBB2, KRAS, EGFR, SMAD4, FGF3/4/19, VEGFA, CCNE1, and GATA4/6, whereas PIK3CA, CCND1, PTEN, NFE2L2, NOTCH1, MLL2, SOX2, FGFR1, and RB1 are altered more frequently in ESCC. 19 TCGARN recently published an elegant study that used genomic analysis to characterize tumors derived from various locations in the esophagus and stomach, largely to better separate EAC and gastric ACs.…”

Increased Risk of Esophageal Cancers Among Men in Taiwan

“…Esophageal cancer is the eighth most common form of cancer and the sixth most frequent common cause of cancer deaths worldwide. The five-year survival rate among patients with esophageal cancer is 19%, decreasing to 0.9% in patients with advanced esophageal cancer [1]. Most patients are initially diagnosed with advanced-stage disease, with fewer diagnosed early enough for successful treatment.…”