PMID- 31925676
OWN - NLM
STAT- MEDLINE
DCOM- 20201110
LR  - 20201110
IS  - 1573-2568 (Electronic)
IS  - 0163-2116 (Linking)
VI  - 65
IP  - 8
DP  - 2020 Aug
TI  - Mutational Mosaics of Cell-Free DNA from Pancreatic Cyst Fluids.
PG  - 2294-2301
LID - 10.1007/s10620-019-06043-1 [doi]
AB  - BACKGROUND: Pancreatic cyst fluids (PCFs) enriched in tumor-derived DNA are a 
      potential source of new biomarkers. The study aimed to analyze germinal variants 
      and mutational profiles of cell-free (cf)DNA shed into the cavity of pancreatic 
      cysts. METHODS: The study cohort consisted of 71 patients who underwent 
      endoscopic ultrasound fine-needle aspiration of PCF. Five malignant cysts, 19 
      intraductal papillary mucinous neoplasms (IPMNs), 11 mucinous cystic neoplasms 
      (MCNs), eight serous cystic neoplasms (SCNs), and 28 pseudocysts were identified. 
      The sequencing of 409 genes included in Comprehensive Cancer Panel was performed 
      using Ion Proton System. The mutation rate of the KRAS and GNAS canonical loci 
      was additionally determined using digital PCR. RESULTS: The number of mutations 
      detected with NGS varied from 0 to 22 per gene, and genes with the most mutations 
      were: TP53, KRAS, PIK3CA, GNAS, ADGRA2, and APC. The frequencies of the majority 
      of mutations did not differ between non-malignant cystic neoplasms and 
      pseudocysts. NGS detected KRAS mutations in malignant cysts (60%), IPMNs (32%), 
      MCNs (64%), SCNs (13%), and pseudocysts (14%), with GNAS mutations in 20%, 26%, 
      27%, 13%, and 21% of samples, respectively. Digital PCR-based testing increased 
      KRAS (68%) and GNAS (52%) mutations detection level in IPMNs, but not other cyst 
      types. CONCLUSIONS: We demonstrate relatively high rates of somatic mutations of 
      cancer-related genes, including KRAS and GNAS, in cfDNA isolated from PCFs 
      irrespectively of the pancreatic cyst type. Further studies on molecular 
      mechanisms of pancreatic cysts malignant transformation in relation to their 
      mutational profiles are required.
FAU - Paziewska, Agnieszka
AU  - Paziewska A
AD  - Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center 
      for Postgraduate Education, Roentgena 5, 02-781, Warsaw, Poland.
AD  - Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 
      5, 02-781, Warsaw, Poland.
FAU - Polkowski, Marcin
AU  - Polkowski M
AD  - Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center 
      for Postgraduate Education, Roentgena 5, 02-781, Warsaw, Poland.
FAU - Goryca, Krzysztof
AU  - Goryca K
AD  - Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 
      5, 02-781, Warsaw, Poland.
AD  - Next Generation Sequencing Core Facility, Centre of New Technologies, University 
      of Warsaw, 02-097, Warsaw, Poland.
FAU - Karczmarski, Jakub
AU  - Karczmarski J
AD  - Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 
      5, 02-781, Warsaw, Poland.
FAU - Wiechowska-Kozlowska, Anna
AU  - Wiechowska-Kozlowska A
AD  - Department of Endoscopy, Ministry of Internal Affairs Hospital, 70-362, Szczecin, 
      Poland.
FAU - Dabrowska, Michalina
AU  - Dabrowska M
AD  - Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 
      5, 02-781, Warsaw, Poland.
FAU - Mikula, Michal
AU  - Mikula M
AD  - Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 
      5, 02-781, Warsaw, Poland.
FAU - Ostrowski, Jerzy
AU  - Ostrowski J
AUID- ORCID: 0000-0003-1363-3766
AD  - Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center 
      for Postgraduate Education, Roentgena 5, 02-781, Warsaw, Poland. 
      jostrow@warman.com.pl.
AD  - Department of Genetics, Maria Sklodowska-Curie Institute-Cancer Center, Roentgena 
      5, 02-781, Warsaw, Poland. jostrow@warman.com.pl.
LA  - eng
GR  - 2012/05/B/NZ5/01539/Narodowe Centrum Nauki/International
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200110
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 (Cell-Free Nucleic Acids)
RN  - 0 (Chromogranins)
RN  - 0 (KRAS protein, human)
RN  - EC 3.6.1.- (GNAS protein, human)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
CIN - Dig Dis Sci. 2020 Aug;65(8):2153-2155. PMID: 32221760
MH  - Adult
MH  - Aged
MH  - Cell-Free Nucleic Acids/*analysis
MH  - Chromogranins/genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - GTP-Binding Protein alpha Subunits, Gs/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pancreatic Cyst/*chemistry/genetics
MH  - Pancreatic Neoplasms/chemistry/*diagnosis/genetics
MH  - Prospective Studies
MH  - Proto-Oncogene Proteins p21(ras)/genetics
MH  - Young Adult
OTO - NOTNLM
OT  - Digital PCR
OT  - GNAS
OT  - KRAS
OT  - Next-generation sequencing
OT  - Pancreatic cyst fluids
EDAT- 2020/01/12 06:00
MHDA- 2020/11/11 06:00
CRDT- 2020/01/12 06:00
PHST- 2019/09/14 00:00 [received]
PHST- 2019/12/31 00:00 [accepted]
PHST- 2020/01/12 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/01/12 06:00 [entrez]
AID - 10.1007/s10620-019-06043-1 [pii]
AID - 10.1007/s10620-019-06043-1 [doi]
PST - ppublish
SO  - Dig Dis Sci. 2020 Aug;65(8):2294-2301. doi: 10.1007/s10620-019-06043-1. Epub 2020 
      Jan 10.