Hereditary Cancer in Clinical Practice |open access: Novel germline MSH2 mutation in Lynch syndrome patient surviving multiple cancers (ovarian cancer as first cancer)

Case report
Hereditary Cancer in Clinical Practice 2012, 10:1 doi:10.1186/1897-4287-10-1
Published: 10 January 2012

Abstract (provisional)

Lynch syndrome (LS) individuals are predisposed to a variety of cancers, most commonly colorectal, uterine, urinary tract, ovarian, small bowel, stomach and biliary tract cancers. The risk of extracolonic manifestations appears to be highest in MSH2 mutations carriers. We present a carrier case with a novel MSH2 gene mutation that clearly demonstrates the broad extent of LS phenotypic expression and highlights several important clinical aspects. Current evidence suggests that colorectal tumors from LS patients tend to have better prognoses than their sporadic counterparts, however survival benefits for other cancers encountered in LS are unclear.
In this article we describe a family with a novel protein truncating mutation of c.2388delT in the MSH2 gene, particularly focusing on one individual carrier affected with multiple primary cancers who is surviving 25 years on. Our report of multiple primary tumors occurring in the 12-25 years interval might suggest these patients do not succumb to other extracolonic cancers, provided they are regularly followed-up.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 "Firstly, the patient over time presented with five primary cancers (in different organs) all of them, except that of breast, typical for the tumor spectrum of LS.   Early-stage ovarian mucinous carcinoma was the first manifestation of LS spectrum in the proband. The lifetime risk of ovarian cancer in Lynch syndrome is approximately 10-12% [12], with higher risks (36%) reported in MSH2 carriers [13]. Recent estimates of age-specific cumulative cancer risks in Lynch syndrome families suggest lower than published elsewhere ovarian cancers risk (24% ovarian cancer risk in MSH2) [14]. MMR-deficient ovarian cancers are biologically and clinically different from BRCA deficient cancers, the former overrepresented by non-serous histology types, early-stage and early-onset disease [12, 15]...."