MEN2 syndrome (RET) testing
Multiple Endocrine Neoplasia Type 2
Multiple endocrine neoplasia Type 2 (MEN2) is a congenital thyroid cancer, caused in most cases by a mutation in the RET proto-oncogene (10q11.2).
MEN2 is a rare disease (affecting about one to nine in a hundred thousand (1–9/100,000)). MEN2 has two subtypes:
multiple endocrine neoplasia type 2A;
multiple endocrine neoplasia type 2B.
In turn, multiple endocrine neoplasia type 2A has several variants:
classical MEN2A;
MEN2A with CLA (Cutaneous lichen amyloidosis);
MEN2A with Hirschsprung’s disease;
FMTC, familial medullary thyroid carcinoma.
MEN2A is more common than MEN2B. MEN2A is diagnosed in approximately 95% of cases.
MEN2 has autosomal dominant heredity, which means that a mutation in one of the chromosomes is sufficient for the disease to manifest. To determine the genetic causes of the disease, the coding part of the RET gene is read and sequenced. In very rare cases, the genetic cause (mutation) of MEN2 may be in another gene, not the RET gene; then a gene panel test must be performed.
Types of molecular testing:
- single-gene Sanger sequencing test (the coding part of the RET gene is sequenced; small insertions/deletions and point mutations can be detected*);
*Large deletions/insertions and inversions in the RET gene are extremely rare. - gene panel test (several genes that may be associated with MEN2 are sequenced by the NGS method).
SIA GenEra offers Sanger sequencing of coding parts of the RET gene (exons and their splicing sites) done in the following manner:
first stage — the reading (sequencing) of the part of the RET gene where mutations are more common (exons: 10 to 16);
second stage — if no mutations are found on the first stage, the remaining RET gene exons are sequenced, or, for the reasons of economy, it is recommended to perform a gene panel analysis.