Introduction. Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic precancerous lesion of pancreatic cancer (PDA). IPMNs can progress from low to high-grade dysplasia, to invasive PDAC, but exact data regarding cancer risks are limited. PDAC is the fourth leading cause of cancer death . The overall 5-year survival is 6%, but survival of patients with early stage PDAC is significantly better. AIM We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with a clinically-oriented bioinformatic interpretation of data to understand what are the most relevant pathways altered in precursor lesions. Materials and methods High resolution cytogenetic analysis was performed in 20 formalin fixed paraffin embedded samples of IPMNs by Oncoscan FFPE assay. Genomic data were analyzed for copy number gains and losses, loss of heterozygosity and for a panel of recurrent somatic mutations. Results were validated by qPCR and FISH analysis. Results Twenty samples, including 14 mixed-type IPMNs (70%), 4 branch-duct IPMNs (20%) and 2 main-duct IPMNs (10%), were collected. We identified micro-invasive carcinoma (< 1 mm) and invasive carcinoma in 25% and in 10% of IPMNs respectively. By our high resolution cytogenetic analysis we observed that 8 IPMNs (40%) presented a nearly normal karyotype (< 4 copy number alterations), while 12 IPMNs (60%) showed a complex karyotype (> 10 alterations). In the latter subgroup were detected specific copy number gains of TERC and c-MYC oncogenes. Interestingly we noticed that TERC and c-MYC overexpression, present in 92% and 45% of complex karyotype samples respectively, were only observed in high-grade IPMNs, suggesting a possible role in a progression to malignancy. Oncoscan data were confirmed by Real Time and FISH analysis. Conclusions Those results suggest a role of TERC and c-MYC overexpression as a possible biomarkers in the early identification of patients with complex karyotype IPMNs in order to better stratification of cystic lesions that could require surgery

Grassi Elisa, D.S. (2017). TERC AND MYC COPY NUMBER GAIN AS POWERFUL GENETIC MARKERS FOR INTRADUCTAL PAPILLARY NEOPLASMS OF THE PANCREAS.

TERC AND MYC COPY NUMBER GAIN AS POWERFUL GENETIC MARKERS FOR INTRADUCTAL PAPILLARY NEOPLASMS OF THE PANCREAS

Grassi Elisa
Writing – Original Draft Preparation
;
Durante Sandra
Membro del Collaboration Group
;
Astolfi Annalisa
Membro del Collaboration Group
;
FREIER, EVA
Membro del Collaboration Group
;
Comito Francesca
Membro del Collaboration Group
;
Frega Giorgio
Membro del Collaboration Group
;
Palloni Andrea
Membro del Collaboration Group
;
Panzacchi Riccardo
Membro del Collaboration Group
;
Santini Donatella
Membro del Collaboration Group
;
Falconi Mirella
Membro del Collaboration Group
;
Teti Gabriella
Membro del Collaboration Group
;
Casadei Riccardo
Membro del Collaboration Group
;
Ricci Claudio
Membro del Collaboration Group
;
Biasco Guido
Membro del Collaboration Group
;
Di Marco Mariacristina
Project Administration
2017

Abstract

Introduction. Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic precancerous lesion of pancreatic cancer (PDA). IPMNs can progress from low to high-grade dysplasia, to invasive PDAC, but exact data regarding cancer risks are limited. PDAC is the fourth leading cause of cancer death . The overall 5-year survival is 6%, but survival of patients with early stage PDAC is significantly better. AIM We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with a clinically-oriented bioinformatic interpretation of data to understand what are the most relevant pathways altered in precursor lesions. Materials and methods High resolution cytogenetic analysis was performed in 20 formalin fixed paraffin embedded samples of IPMNs by Oncoscan FFPE assay. Genomic data were analyzed for copy number gains and losses, loss of heterozygosity and for a panel of recurrent somatic mutations. Results were validated by qPCR and FISH analysis. Results Twenty samples, including 14 mixed-type IPMNs (70%), 4 branch-duct IPMNs (20%) and 2 main-duct IPMNs (10%), were collected. We identified micro-invasive carcinoma (< 1 mm) and invasive carcinoma in 25% and in 10% of IPMNs respectively. By our high resolution cytogenetic analysis we observed that 8 IPMNs (40%) presented a nearly normal karyotype (< 4 copy number alterations), while 12 IPMNs (60%) showed a complex karyotype (> 10 alterations). In the latter subgroup were detected specific copy number gains of TERC and c-MYC oncogenes. Interestingly we noticed that TERC and c-MYC overexpression, present in 92% and 45% of complex karyotype samples respectively, were only observed in high-grade IPMNs, suggesting a possible role in a progression to malignancy. Oncoscan data were confirmed by Real Time and FISH analysis. Conclusions Those results suggest a role of TERC and c-MYC overexpression as a possible biomarkers in the early identification of patients with complex karyotype IPMNs in order to better stratification of cystic lesions that could require surgery
2017
TERC AND MYC COPY NUMBER GAIN AS POWERFUL GENETIC MARKERS FOR INTRADUCTAL PAPILLARY NEOPLASMS OF THE PANCREAS
Grassi Elisa, D.S. (2017). TERC AND MYC COPY NUMBER GAIN AS POWERFUL GENETIC MARKERS FOR INTRADUCTAL PAPILLARY NEOPLASMS OF THE PANCREAS.
Grassi Elisa, Durante Sandra, Astolfi Annalisa, Eva Freier, Comito Francesca, Frega Giorgio, Palloni Andrea, Panzacchi Riccardo, Santini Donatella, Fa...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/628929
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