Abstract
Mitogen-activated protein kinase kinase 1 (MAP2K1)
is a dual specificity protein kinase that phosphorylates both threonine and tyrosine residues in
ERK
.
MAP2K1
mutations have been identified in several cancers. However, their role in Middle Eastern papillary thyroid cancer (PTC) and colorectal cancer (CRC) is lacking. In this study, we evaluated the prevalence of
MAP2K1
mutations in a large cohort of Middle Eastern PTC and CRC using whole-exome and Sanger sequencing technology. In the discovery cohort of 100 PTC and 100 CRC cases (comprising 50
MAPK
mutant and 50
MAPK
wildtype cases each), we found one
MAP2K1
mutation each in PTC and CRC, both of which were
MAPK
wildtype. We further analyzed 286 PTC and 289 CRC
MAPK
wildtype cases and found three
MAP2K1
mutant PTC cases and two
MAP2K1
mutant CRC cases. Thus, the overall prevalence of
MAP2K1
mutation in
MAPK
wildtype cases was 1.1% (4/336) in PTC and 0.9% (3/339) in CRC. Histopathologically, three of the four
MAP2K1
mutant PTC cases were follicular variant and all four tumors were unifocal with absence of extra-thyroidal extension. All the three CRC cases harboring
MAP2K1
mutation were of older age (> 50 years) and had moderately differentiated stage II/III tumors located in the left colon. In conclusion, this is the first comprehensive report of
MAP2K1
somatic mutations prevalence in PTC and CRC from this ethnicity. The mutually exclusive nature of
MAP2K1
and
MAPK
mutations suggests that each of these mutation may function as an initiating mutation driving tumorigenesis through
MAPK
signaling pathway.