Karyotypic abnormalities in tumours of the pancreas

Abstract

Summary Short-term cultures from 20 pancreatic tumours, three endocrine and 17 exocrine, were cytogenetically analysed. All three endocrine tumours had a normal chromosome complement. Clonal chromosome aberrations were detected in 13 of the 17 exocrine tumours: simple karyotypic changes were found in five carcinomas and numerous numerical and/or structural changes in eight. When the present findings and those previously reported by our group were viewed in conjunction, the most common numerical imbalances among the 22 karyotypically abnormal pancreatic carcinomas thus available for evaluation turned out to be, in order of falling frequency, -18, -Y, + 20, + 7, + 11 and -12. Imbalances brought about by structural changes most frequently affected chromosomes I (losses in lp but especially gains of lq), 8 (in particular 8q gains but also 8p losses), and 17 (mostly 17q gain but also loss of 17p). Chromosomal bands lp32, 1q1O, 6q21, 7p22, 8p2l, 8ql 1, 14pl 1, l5q10-1 1, and 17qll were the most common breakpoint sites affected by the structural rearrangements. Abnormal karyotypes were detected more frequently in poorly differentiated and anaplastic carcinomas than in moderately and well differentiated tumours.Pancreatic carcinoma accounts for about 10% of malignancies of the digestive organs and the outcome is fatal in more than 95% of the cases.

Cytogenetic and FISH analyses of pancreatic carcinoma reveal breaks in 18q11 with consistent loss of 18q12-qter and frequent gain of 18p

“…nullisomy for 18q material was not seen. The observed frequent loss of 18q is in agreement with earlier cytogenetic (Johansson et al, 1992;Bardi et al, 1993;Griffin et al, 1994Griffin et al, , 1995, CGH (Fukushige et al, 1997;Mahlamaki et al, 1997) and LOH studies (Hahn et al, 1995). In the ten cases in which losses of 18q occurred through breaks in the q arm, the breakpoints were localized using both YAC and pcpl8q probes.…”

“…The clustering of breaks close to the centromere indicates that loss of genes in bands 18q11 and 18q12, in addition to those located in 18q21, e.g. DPC4 and DCC, are important in the development of pancreatic tumours.Keywords: chromosome 18; pancreatic carcinoma; deletions Although only a handful of larger series of cytogenetically investigated pancreatic carcinomas have been reported, several frequent recurrent chromosomal imbalances, such as trisomy 7 and 20, monosomy 18, loss of Ip, 3p, 6q, 8p, 9p, 17p and 19p, and gain of lq, 3q, 8q, 1 lq, 19q and 20q, have been identified (Johansson et al, 1992;Bardi et al, 1993;Griffin et al, 1994Griffin et al, , 1995Gorunova et al, 1998). The pattern of cytogenetic imbalances seems characteristic for pancreatic cancer, albeit many of the individual changes are also found in other solid tumours (Mertens et al, 1997).…”

“…In some of the frequently deleted regions, a concomitant inactivation of a tumour-suppressor gene (TSG) on the remaining normal chromosome has been shown, i.e. CDKN2A in 9p2l Bartsch et al, 1995), BRCA2 in 13q12 (Goggins et al, 1996), TP53 in 17pl3 (Ruggeri et al, 1992;Scarpa et al, 1993) and SMAD4 (DPC4) in 18q21 , whereas the TSGs in the other loci remain to be identified.The most common chromosome aberration in pancreatic cancer is monosomy 18 (Johansson et al, 1992;Bardi et al, 1993;Griffin et al, 1994Griffin et al, , 1995. However, recent cytogenetic (Gorunova et al, 1998) and comparative genomic hybridization (CGH) analyses (Mahlamaki et al, 1997) have also revealed frequent partial deletions of 18q.…”

“…The most common chromosome aberration in pancreatic cancer is monosomy 18 (Johansson et al, 1992;Bardi et al, 1993;Griffin et al, 1994Griffin et al, , 1995. However, recent cytogenetic and comparative genomic hybridization (CGH) analyses (Mahlamaki et al, 1997) have also revealed frequent partial deletions of 18q.…”

Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer

“…In this respect. it is worthy of note that no structural abnormality of chromosome 5 had been reported in the nine ampullary or periampullary carcinomas in which cytogenetic analysis was performed (Johansson et al 1992: Bardi et al 1993. Molecular techniques are more sensitive than cytogenetic analysis in detecting loss of genetic material.…”