CYTOGENETIC ANALYSIS OF PANCREATIC CARCINOMAS - INTRATUMOR HETEROGENEITY AND NONRANDOM PATTERN OF CHROMOSOME-ABERRATIONS

Twenty-nine nonendocrine pancreatic carcinomas (20 primary tumors and nine metastases) were studied by chromosome banding after short-term c ulture. Acquired clonal aberrations were found in 25 tumors and a deta iled analysis of these revealed extensive cytogenetic intratumor heter ogeneity. Apart from six carcinomas with one clone only, 19 tumors dis played from two to 58 clones, bringing the total number of clones to 2 30. Karyotypically related clones, signifying evolutionary variation, were found in 16 tumors, whereas unrelated crones were present in nine , the latter finding probably reflecting a distinct pathogenetic mecha nism. The cytogenetic profile of pancreatic carcinoma was characterize d by multiple numerical and structural changes. In total, more than 50 0 abnormal chromosomes, including rings, markers, homogeneously staine d regions, and double minutes, altogether displaying 608 breakpoints, were detected. This complexity and heterogeneity notwithstanding, a no nrandom karyotypic pattern can be discerned in pancreatic cancer. Chro mosomes 1,3, 6, 7, 8, 11, 12, 17, and 19 and bands 1q12, 1q21, 3q11, 6 p21, 6q21, 7q11, 7q22, 7q32, 11q13, 13cen, 14cen, 17q11, 17q21, and 19 q13 were most frequently involved in structural rearrangements. A tota l of 19 recurrent unbalanced structural changes were identified, Il of which were not reported previously: del(1)(q11), del(3)(p11), i(3)(q1 0), del(4)(q25), del(11)(p13), dup(11)(q13q23), i(12)(p10), der(13;15) (q10;q10), del(18)(q12), del(18)(q21), and i(19)(q10). The main karyot ypic imbalances were entire-copy losses of chromosomes 18, Y, and 21,g ains of chromosomes 7, 2, and 20, partial or whole-arm losses of 1p, 3 p, 6q, 8p, 9p, 15q, 17p, 18q, 19p, and 20p, and partial or whole-arm g ains of 1q, 3q, 5p, 6p, 7q, 8q, 11q, 12p, 17q, 19q, and 20q. In genera l, the karyotypic pattern of pancreatic carcinoma fits the multistep c arcinogenesis concept. The observed cytogenetic heterogeneity appears to reflect a multitude of interchangeable but oncogenetically equivale nt events, and the nonrandomness of the chromosomal alterations unders cores the preferential pathways involved in tumor initiation and progr ession. (C) 1998 Wiley-Liss, Inc.