IDENTIFICATION OF A NEW CHROMOGRANIN-B FRAGMENT(314-365) IN ENDOCRINETUMORS

A rabbit antiserum was raised against the fragment (350-365) of human chromogranin B corresponding to the C-terminal end of a putative prote olytic fragment generated by the cleavage of a dibasic doubler located in position 366-367 of the precursor. A radioimmunoassay was develope d. Chromatographic analysis of 10 endocrine tumor extracts (one liver metastasis of a gastrinoma, one liver metastasis of a medullary carcin oma of the thyroid, one VIPoma, one insulinoma, one nonsecreting pancr eatic endocrine tumor, one local recurrence of a gut carcinoid, two pi tuitary gonadotropinoma, and two nonsecreting pituitary adenomas) reve aled the presence of two forms of immunoreactive material. The most ab undant form had an apparent molecular weight of 4500 and was purified to homogeneity by successive reverse-phase HPLC chromatographies and p artially sequenced. The N-terminal sequence of the peptide, establishe d by automated Edman degradation, was A-S-E-E-E-P-E-Y-G-E-E-I-K-G-Y-P- G-V-Q and corresponded to the 314-332 sequence of human chromogranin B . Taking into account the specificity of the antiserum used for peptid e identification, we deduced that the purified peptide was chromograni n B(314-365) and represented a new form generated by limited proteolys is of chromogranin B.