Genomic Alterations in Tumor Stroma

Abstract

It was traditionally believed that the tumor was the seed that lay in the passive soil of the microenvironment, with the latter providing ''permissive elements'' for the tumor to grow and invade. Subsequently, it was recognized that both neoplasia and its microenvironment interacted as equal partners. Recent advances addressing genomic alterations in the tumor microenvironment, relevant to clinical outcome and treatment choices, are summarized. These include microenvironmental genomic alterations not only in different solid tumors, but also, rather surprisingly, in inflammatory bowel disease. These observations promise new biomarkers of prognosis and a new compartment to target therapy.

Role of cancer-associated fibroblasts in breast cancer development and prognosis

“…On the other hand, the presence of somatic genetic alterations in active fibroblasts remains controversial (Campbell et al, 2009;Eng et al, 2009). While several groups reported the presence of mutations only in cancer epithelial cells, chromosomal loss of heterozygosity (LOH) and mutations have also been reported in CAFs by other groups (Campbell et al, 2011;Eng et al, 2009).…”

Prevalence ofPIK3CAmutations and the SNP rs17849079 in Arab breast cancer patients

“…[4][5][6][7] However, in recent years, genetic and epigenetic alterations have been also reported in stromal cells such as carcinoma-associated fibroblasts (CAFs) that may play a role in human carcinogenesis. 8,9 Carcinomas initiate and progress due to genetic and epigenetic alterations in epithelial cells. However, recently, these alterations have also been reported in stromal fibroblasts.…”

Stromal epigenetic dysregulation is sufficient to initiate mouse prostate cancer via paracrine Wnt signaling

“…Despite certain genetic alterations found in stromal cells from various cancers (8), the absence of detectable genetic changes has been described in CAFs from breast and ovarian carcinomas, accompanied by dramatic changes in expression of genes encoding secreted or cell surface proteins (9,10). Despite their tumor-promoting function, it has been reported that CAFs generally lack cell-intrinsic oncogenic properties (11).…”