Marker Designation
Alias
Gene Location

Indications

NK2 homeobox 1 (NKX2-1)

BCH • BHC • NK-2 • TEBP • thyroid transcription factor-1 (TTF1, TTF-1) • NKX2A • TITF1 • NKX2.1

Location: 14q13

NK2 homeobox 1 (Nkx2.1) encodes a homeodomain transcription factor whose expression is restricted to the thyroid, lung and specific regions of the forebrain and plays a key role in the development of these organs. In lung epithelial cells, two regions of promoter activity, designated as proximal and distal promoters, map to DNA elements located upstream of exons 1 and 2 (within intron 1). That both promoters are active in vivo has been demonstrated by the presence of multiple Nkx2.1 mRNA species with distinct and appropriate exonic composition.

Because the mechanisms of Nkx2.1 tissue selective gene expression remain entirely unknown, investigators at Women's and Children's Hospital, USC School of Medicine ( Los Angeles, CA) examined the potential of three overlapping DNA fragments, representing a total of approximately 4 kb of potential regulatory DNA from the baboon Nkx2.1 5' flanking region to direct expression of LacZ in transgenic mice during embryonic development. The three constructs include sequences in proximal, distal and both promoters separately. All three fragments directed LacZ expression to the brain of transgenic E15 and E18 mouse embryos. In addition to a number of other sites, all three constructs were active in subgroups of cells localized in the hypothalamus, a well-established site of endogenous Nkx2.1 gene expression. Two of the fragments conferred tracheal epithelial-specific LacZ gene expression, but parenchymal lung expression was not observed. None of the three fragments had activity in the thyroid. These data demonstrate the complexity of the Nkx2.1 tissue specific gene regulation and suggest that cis-active elements required for tracheal versus lung morphogenesis may be distinct. The same applies to the brain, which provides the most permissive environment for recognition of Nkx2.1 tissue specific cis-active elements (Pan Q, etal, Gene, 18 Apr 2004;331:73-82).  

- lung cancer

SHC (Src homology 2 domain containing) transforming protein 1 (SHC1)

SHC, Shc • p66 • SHCA • p52SHC • p66SHC • FLJ26504

Location: 1q21

The Shc proteins are involved in a number of well documented cellular pathways that are correlated with tumor aggressiveness across many types of cancer, offering a broad opportunity for clinical testing.  

Thymidylate synthetase (TYMS)

HsT422 • TMS • TS • TSase • TYSY

Location: 18p11.32

Thymidylate synthase (TYMS) is the key enzyme involved in the de novo synthesis of thymidine and subsequently DNA synthesis. The reaction catalyzed by TYMS is the methylation of dUMP to dTMP, an essential precursor for DNA, with the transferred methyl group provided by the cofactor methylenetetrahydrofolate (Montfort WR and Weichsel A, Pharmacol Ther, Oct-Dec 1997;76(1-3):29-43). A specific interaction has also been shown to exist between oncogenes and TYMS with TYMS protein binding to the p53 and c-myc RNA, and wild-type p53 inhibiting TYMS promotor activity. The clinical implications of the interactions between oncogenes and TYMS are as yet unclear, with the results of some studies in this regard being contradictive (Van Triest B, etal, Ann Oncol, Apr 2000;11(4):385-91).