Identification of a new chromogranin B fragment (314-365) in endocrine tumors.

A rabbit antiserum was raised against the fragment (350-365) of human chromogranin B corresponding to the C-terminal end of a putative proteolytic fragment generated by the cleavage of a dibasic doublet located in position 366-367 of the precursor. A radioimmunoassay was developed. Chromatographic analysis of 10 endocrine tumor extracts (one liver metastasis of a gastrinoma, one liver metastasis of a medullary carcinoma of the thyroid, one VIPoma, one insulinoma, one nonsecreting pancreatic endocrine tumor, one local recurrence of a gut carcinoid, two pituitary gonadotropinoma, and two non-secreting pituitary adenomas) revealed the presence of two forms of immunoreactive material. The most abundant form had an apparent molecular weight of 4500 and was purified to homogeneity by successive reverse-phase HPLC chromatographies and partially sequenced. The N-terminal sequence of the peptide, established by automated Edman degradation, was A-S-E-E-E-P-E-Y-G-E-E-I-K-G-Y-P-V-Q and corresponded to the 314-332 sequence of human chromogranin B. Taking into account the specificity of the antiserum used for peptide identification, we deduced that the purified peptide was chromogranin B(314-365) and represented a new form generated by limited proteolysis of chromogranin B.