PMID- 34614142
OWN - NLM
STAT- MEDLINE
DCOM- 20220629
LR  - 20240102
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 146
IP  - 7
DP  - 2022 Jul 1
TI  - BRAF Rearrangements and BRAF V600E Mutations Are Seen in a Subset of Pancreatic 
      Carcinomas With Acinar Differentiation.
PG  - 840-845
LID - 10.5858/arpa.2020-0739-OA [doi]
AB  - CONTEXT.-: Comprehensive genomic profiling has demonstrated that approximately 
      20% of pancreatic carcinomas with acinar differentiation harbor potentially 
      targetable BRAF fusions that activate the MAPK pathway. OBJECTIVES.-: To validate 
      the above finding by BRAF break-apart fluorescence in situ hybridization (FISH) 
      in a large series of pure acinar cell carcinomas (ACCs), evaluate tumors for the 
      presence of BRAF V600E mutations, and compare clinicopathologic features of 
      tumors with BRAF rearrangements with those without. DESIGN.-: Thirty cases of 
      pure ACC and 6 cases of mixed acinar-neuroendocrine carcinoma (ACC-NEC) were 
      retrieved. A break-apart FISH probe was used to detect BRAF rearrangements. 
      Immunohistochemistry for BRAF V600E was performed. RESULTS.-: BRAF rearrangements 
      by FISH were found in 6 of 36 cases (17%), 5 of which were pure ACC and 1 was a 
      mixed ACC-NEC. Follow-up was available in 29 of 36 cases (81%). The median 
      survival was 22 months for BRAF-rearranged cases and 16 months for BRAF-intact 
      cases; the 2-year overall survival was 50% for BRAF-rearranged cases and 35% for 
      BRAF-intact cases. No significant clinicopathologic differences were identified 
      in cases with BRAF rearrangement compared with those without BRAF rearrangement. 
      BRAF V600E mutation was identified in 2 of 34 cases (6%), both of which were pure 
      ACC and were BRAF-intact by FISH. CONCLUSIONS.-: This study supports the finding 
      that BRAF rearrangements are present in approximately 20% of cases and identified 
      BRAF V600E mutations in approximately 5% of cases. These cases may benefit from 
      targeted therapy.
FAU - Ghosh, Toshi
AU  - Ghosh T
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
FAU - Greipp, Patricia T
AU  - Greipp PT
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
FAU - Knutson, Darlene
AU  - Knutson D
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
FAU - Kloft-Nelson, Sara
AU  - Kloft-Nelson S
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
FAU - Jenkins, Sarah
AU  - Jenkins S
AD  - From the Department of Health Sciences Research (Jenkins), Mayo Clinic, 
      Rochester, Minnesota.
FAU - Mounajjed, Taofic
AU  - Mounajjed T
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
FAU - Said, Samar
AU  - Said S
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
FAU - La Rosa, Stefano
AU  - La Rosa S
AD  - From the Institute of Pathology, Lausanne University Hospital and University of 
      Lausanne, Lausanne, Switzerland (La Rosa).
FAU - Vanoli, Alessandro
AU  - Vanoli A
AD  - From the Anatomic Pathology Unit, Department of Molecular Medicine, University of 
      Pavia, and IRCCS San Matteo Hospital, Pavia, Italy (Vanoli).
FAU - Sessa, Fausto
AU  - Sessa F
AD  - From the Anatomic Pathology Unit, Department of Medicine and Surgery, University 
      of Insubria, Varese, Italy (Sessa).
FAU - Naini, Bita V
AU  - Naini BV
AD  - From the Department of Pathology, University of California, Los Angeles (Naini).
FAU - Bellizzi, Andrew
AU  - Bellizzi A
AD  - From the Department of Pathology, University of Iowa, Iowa City (Bellizzi).
FAU - Zhang, Lizhi
AU  - Zhang L
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
FAU - Kerr, Sarah E
AU  - Kerr SE
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
FAU - Graham, Rondell P
AU  - Graham RP
AD  - From the Department of Laboratory Medicine and Pathology (Ghosh, Greipp, Knutson, 
      Kloft-Nelson, Mounajjed, Said, Zhang, Kerr, Graham), Mayo Clinic, Rochester, 
      Minnesota.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - *Carcinoma, Acinar Cell/genetics/pathology
MH  - *Carcinoma, Neuroendocrine/genetics/pathology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Mutation
MH  - *Pancreatic Neoplasms/genetics/pathology
MH  - Proto-Oncogene Proteins B-raf/genetics
EDAT- 2021/10/07 06:00
MHDA- 2022/06/30 06:00
CRDT- 2021/10/06 17:31
PHST- 2021/06/03 00:00 [accepted]
PHST- 2021/10/07 06:00 [pubmed]
PHST- 2022/06/30 06:00 [medline]
PHST- 2021/10/06 17:31 [entrez]
AID - 471495 [pii]
AID - 10.5858/arpa.2020-0739-OA [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2022 Jul 1;146(7):840-845. doi: 10.5858/arpa.2020-0739-OA.