EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis

Abstract

Background: Ephrin receptor B2 (EPHB2) has recently been proposed as a novel tumor suppressor gene in colorectal cancer (CRC). Inactivation of the gene has been shown to correlate with progression of colorectal tumorigenesis, and somatic mutations have been reported in both colorectal and prostate tumors.

Evidence of linkage to chromosomes 10p15.3–p15.1, 14q24.3–q31.1 and 9q33.3–q34.3 in non-syndromic colorectal cancer families

“…Locations for genes known to be causative for known syndromes are shown as vertical lines. The dotted vertical lines indicate the locations of genes known or suspected to be causative for established familial CRC syndromes or from other GWLS or GWAS: (1) EPHB2, 34 Linkage to colorectal cancer on 10p, 14q and 9q…”

Regulation and misregulation of Eph/ephrin expression

“…The EphB2 gene has been implicated as a tumor suppressor gene altered in both prostate cancer and colorectal cancer. 79 Huusko and colleagues 80 reported that the DU 145 prostate cancer cell line carries a truncating mutation of ephB2 and a deletion of the remaining allele. This truncated version was subject to Nonsense-Mediated Decay (NMD).…”

Germline Genetics in Colorectal Cancer Susceptibility and Prognosis

“…The inheritance pattern of HPP is not well defined, but a few characterized families show possible recessive inheritance (Young & Jass, 2006). A germline mutation in EPHB2 was identified in an individual who had more than 100 hyperplastic polyps, but EPHB2 mutations have not been observed in other HPP cases (Kokko et al, 2006). Thus, the causal genes for most individuals with HPP have yet to be identified.…”