Lynch syndrome: five unanswered questions - Commentary

open access

"A large proportion of deaths in LS are associated with extra-colonic and extra-endometrial cancers."

Despite the great advances that have occurred in the century following the first description of a Lynch syndrome (LS) family and more especially, in more than 20 years since the discovery of causal mutations in the mismatch repair genes (MMR), long-standing clinical questions remain unanswered. Moreover, as a result of novel technologies, new questions have arisen. With this commentary, we aim to briefly cover some of these aspects of LS. We will focus on current challenges regarding the definition of LS-related tumors, their prevention and early detection, the role of next-generation sequencing (NGS) in the molecular diagnostics of LS and advances in the treatment of LS tumors.

"Although LS was initially thought of as a colorectal cancer (CRC) syndrome, the established spectrum of LS-associated tumors includes endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, and brain (Turcot syndrome) tumors, sebaceous gland adenomas and keratoacanthomas (Muir–Torre syndrome), and carcinoma of the small bowel [1]."

Tumor spectrum of LS: is there a risk for breast cancer?

 

Can LS-associated cancers be diagnosed early or prevented?

 

Should all colorectal and endometrial carcinomas be tested for MMR 

proteins?

Are we ready to properly implement NGS into the diagnostics of LS?

 

Should treatment of cancer be influenced by MMR status?