Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations
Abstract
Background: The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background. Methods: A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed.
Of the 22 patients surviving for more than five years, 6 went on to develope SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing (NGS) in germline DNA from 20 of these patients.
Results: Of all the radically resected PDAC patients, 6 patients went on to develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which that included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer and urinary bladder cancer, was 52.5 months.
At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 NGS-analyzed patients.
One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, three patients (19%) carried germline mutation(s) in the MLH1+ATM, CHEK2, and RAD51D gene, respectively.
Conclusion: This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis.