PLA2G2A – Colorectal Cancer

Limited evidence supports an association between PLA2G2A and colorectal cancer. In a screen of 14 familial adenomatous polyposis (FAP) and 20 sporadic colorectal cancer patients, no germline PLA2G2A alterations were found in FAP, whereas one sporadic case harbored a heterozygous germline c.144_145del (p.Cys48fs) with somatic loss of the wild-type allele in the tumor (n = 1 proband) (PMID:9272153). No additional unrelated cases or segregation data have been reported.

Structural and enzymatic analyses of PLA2G2A mutants—including the active-site H48Q and membrane-binding V3W/F5W variants—confirm key catalytic features and membrane interactions of the protein (PMID:12501175; PMID:17029400), but no in vitro or in vivo colorectal cancer-specific functional models have been described. Together, these findings provide only Limited support for PLA2G2A as a colorectal cancer predisposition gene. Further replication in larger cohorts and tumor models is needed for clinical utility.

Key Take-home: Current data are insufficient to recommend PLA2G2A screening in colorectal cancer patients.

References

• Human genetics • 1997 • Loss of the PLA2G2A gene in a sporadic colorectal tumor of a patient with a PLA2G2A germline mutation and absence of PLA2G2A germline alterations in patients with FAP. PMID:9272153
• Biochemistry • 2002 • The crystal structure of the H48Q active site mutant of human group IIA secreted phospholipase A2 at 1.5 A resolution provides an insight into the catalytic mechanism. PMID:12501175
• Biochemistry • 2006 • Structural and functional effects of tryptophans inserted into the membrane-binding and substrate-binding sites of human group IIA phospholipase A2. PMID:17029400

Evidence Based Scoring (AI generated)