• Something wrong with this record ?

Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations

M. Lovecek, M. Janatova, P. Skalicky, T. Zemanek, R. Havlik, J. Ehrmann, O. Strouhal, P. Zemankova, K. Lhotova, M. Borecka, J. Soukupova, H. Svebisova, P. Soucek, V. Hlavac, Z. Kleibl, C. Neoral, B. Melichar, B. Mohelnikova-Duchonova,

. 2019 ; 11 (-) : 599-609. [pub] 20190110

Language English Country New Zealand

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc19013458

Grant support
NV16-28375A MZ0 CEP Register

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. Patients and 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 >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients. Results: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which 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 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19013458
003      
CZ-PrNML
005      
20190411095327.0
007      
ta
008      
190405s2019 nz f 000 0|eng||
009      
AR
024    7_
$a 10.2147/CMAR.S185352 $2 doi
035    __
$a (PubMed)30666157
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a nz
100    1_
$a Lovecek, Martin $u Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic.
245    10
$a Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations / $c M. Lovecek, M. Janatova, P. Skalicky, T. Zemanek, R. Havlik, J. Ehrmann, O. Strouhal, P. Zemankova, K. Lhotova, M. Borecka, J. Soukupova, H. Svebisova, P. Soucek, V. Hlavac, Z. Kleibl, C. Neoral, B. Melichar, B. Mohelnikova-Duchonova,
520    9_
$a 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. Patients and 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 >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients. Results: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which 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 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 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.
655    _2
$a časopisecké články $7 D016428
700    1_
$a Janatova, Marketa $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Skalicky, Pavel $u Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic.
700    1_
$a Zemanek, Tomas $u Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic, d.beatrice@seznam.cz.
700    1_
$a Havlik, Roman $u Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic.
700    1_
$a Ehrmann, Jiri $u Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic.
700    1_
$a Strouhal, Ondrej $u Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic, d.beatrice@seznam.cz.
700    1_
$a Zemankova, Petra $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Lhotova, Klara $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Borecka, Marianna $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Soukupova, Jana $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Svebisova, Hana $u Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic, d.beatrice@seznam.cz.
700    1_
$a Soucek, Pavel $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen Czech Republic.
700    1_
$a Hlavac, Viktor $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen Czech Republic.
700    1_
$a Kleibl, Zdenek $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Neoral, Cestmir $u Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic.
700    1_
$a Melichar, Bohuslav $u Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic, d.beatrice@seznam.cz.
700    1_
$a Mohelnikova-Duchonova, Beatrice $u Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic, d.beatrice@seznam.cz.
773    0_
$w MED00165412 $t Cancer management and research $x 1179-1322 $g Roč. 11, č. - (2019), s. 599-609
856    41
$u https://pubmed.ncbi.nlm.nih.gov/30666157 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20190405 $b ABA008
991    __
$a 20190411095344 $b ABA008
999    __
$a ind $b bmc $g 1392768 $s 1051763
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 11 $c - $d 599-609 $e 20190110 $i 1179-1322 $m Cancer management and research $n Cancer manag. res. $x MED00165412
GRA    __
$a NV16-28375A $p MZ0
LZP    __
$a Pubmed-20190405

Find record

Citation metrics

Archiving options