Variant Transcript of ROR1 ENST00000545203 Does Not Encode ROR1 Protein.

Drs. John and Ford reported in that a variant transcript encoding receptor tyrosine kinase-like orphan receptor 1 (ROR1), namely ENST00000545203 or variant 3 (), was a predominant transcript of neoplastic or normal cells in the Bioinformatic database, including GTEx and the 33 datasets from TCGA. Unlike the full-length transcript, Drs. John and Ford deduced that encoded a cytoplasmic ROR1 protein lacking an apparent signal peptide necessary for transport to the cell surface, which they presumed made it unlikely to function as a surface receptor for Wingless/Integrated (Wnt) factors. Moreover, they speculated that studies evaluating ROR1 via immunohistochemistry using any one of several anti-ROR1 mAbs actually may have detected cytoplasmic protein encoded by and that anti-cancer therapies targeting surface ROR1 thus would be ineffective against "cytoplasmic ROR1-positive" cancers that express predominately . We generated lentivirus vectors driving the expression of full-length or the upstream of an internal ribosome entry site (IRES) of the gene encoding a red fluorescent reporter protein. Although we find that cells that express have surface and cytoplasmic ROR1 protein, cells that express neither have surface nor cytoplasmic ROR1, which is consistent with our finding that lacks an in-frame initiation codon for ribosomal translation into protein. We conclude that the detection of ROR1 protein in various cancers cannot be ascribed to the expression of .