Array comparative genomic hybridization of 18 pancreatic ductal adenocarcinomas and their autologous metastases.
BACKGROUND
Mortality rates of pancreatic cancer remain high, which is mainly due to advanced disease and metastasis. We hypothesized that genomic copy number alterations are enriched in metastatic cells compared to autologous primary tumors, which may inform on cancer-related pathways possibly serving as potential targets for specific therapies. We investigated 18 pancreatic ductal adenocarcinomas, including 39 lymph node and 5 distant metastases after surgical resection. Analysis was performed with array-based comparative genomic hybridization (aCGH).


RESULTS
Metastases acquire a higher frequency of copy number alterations with the highest in distant metastasis (median = 42, lymph node metastases: median = 23, primary tumors: median = 17). In lymph node metastases, gains were prevalent on chromosome bands 8q11.23-q24.3, 12q14.1, 17p12.1, 21q22.12, and losses on 3p21.31, 4p14, 8p23.3-p11.21,17p12-11.2. Genes on amplified regions are involved in cancer-related pathways such as WNT-signaling, also involved in metastasis.


CONCLUSIONS
Pancreatic cancers show a high degree of intratumor heterogeneity, which could lead to resistance of chemotherapy and worse outcome. ACGH analysis reveals regions preferentially gained or lost in synchronous metastases encoding for genes involved in cancer-related pathways, which could lead to novel therapeutic opportunities.
['Rausch|Valentin|V|http://orcid.org/0000-0001-7987-5173', 'Krieg|Andreas|A|', 'Camps|Jordi|J|', 'Behrens|Bianca|B|', 'Beier|Manfred|M|', 'Wangsa|Darawalee|D|', 'Heselmeyer-Haddad|Kerstin|K|', 'Baldus|Stephan E|SE|', 'Knoefel|Wolfram T|WT|', 'Ried|Thomas|T|', 'Stoecklein|Nikolas H|NH|']
D000230:Adenocarcinoma D000328:Adult D000368:Aged D000369:Aged, 80 and over D021441:Carcinoma, Pancreatic Ductal D055028:Comparative Genomic Hybridization D056915:DNA Copy Number Variations D006801:Humans D008207:Lymphatic Metastasis D008875:Middle Aged D010190:Pancreatic Neoplasms D019683:Penetrance
Pancreatic cancer aCGH Array-CGH Intratumor hetereogeneity PDAC Pancreatic metastases