PMID- 28984674
OWN - NLM
STAT- MEDLINE
DCOM- 20190226
LR  - 20190226
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 42
IP  - 2
DP  - 2018 Feb
TI  - Targeted Genomic Profiling Reveals Recurrent KRAS Mutations in Mesonephric-like
      Adenocarcinomas of the Female Genital Tract.
PG  - 227-233
LID - 10.1097/PAS.0000000000000958 [doi]
AB  - Mesonephric adenocarcinoma most commonly arises in the cervix and is presumed to 
      be derived from normal or hyperplastic mesonephric remnants. It is characterized 
      by recurrent KRAS mutations and lack of PIK3CA/PTEN alterations. Adenocarcinomas 
      of the uterine corpus and ovary characterized by morphologic and immunophenotypic
      similarities to mesonephric adenocarcinoma have been reported. The pathogenesis
      of these tumors, which have been designated "mesonephric-like adenocarcinomas" is
      unknown, and it has been debated whether these represent mesonephric
      adenocarcinomas that arise in the endometrium/ovary or endometrioid
      adenocarcinomas that closely mimic mesonephric adenocarcinoma. The relationship
      at the molecular level between mesonephric adenocarcinomas and mesonephric-like
      adenocarcinomas is unknown. The aim of this study was to examine the molecular
      alterations in mesonephric-like adenocarcinomas to identify driver mutations and 
      potential therapeutically targetable mutations, and to determine the relationship
      between mesonephric-like adenocarcinomas and mesonephric adenocarcinomas using
      targeted next-generation sequencing. Seven mesonephric-like adenocarcinomas (4
      ovarian, 3 uterine corpus) underwent targeted next-generation sequencing to
      detect mutations, copy number variations and structural variants in exonic
      regions of 300 cancer genes, and 113 selected intronic regions across 35 genes.
      All 7 tumors (100%) harbored canonical activating KRAS mutations (4 G12D, 3
      G12V). PIK3CA activating mutations were identified in 3 of 7 (43%) cases. There
      were no alterations in PTEN, ARID1A, or TP53 in any of the tumors. In copy number
      analysis, 5 of 7 (71%) tumors exhibited 1q gain, which was accompanied by 1p loss
      in 2 cases. In addition, 4 of 7 (57%) tumors had chromosome 10 gain, which was
      accompanied by gain of chromosome 12 in 3 cases. Mesonephric-like
      adenocarcinomas, similar to mesonephric adenocarcinomas, are characterized by
      recurrent KRAS mutations, gain of 1q, lack of PTEN mutations, and gains of
      chromosomes 10 and 12. PIK3CA mutations, which have not previously been
      identified in mesonephric adenocarcinoma, were found in 3 of 7 (43%)
      mesonephric-like adenocarcinomas in our study. Mesonephric-like adenocarcinomas
      exhibit strikingly similar molecular aberrations to mesonephric adenocarcinomas, 
      but also frequently harbor PIK3CA mutations, demonstrating biological overlap
      with carcinomas of both mesonephric and Mullerian (endometrioid) differentiation.
      Given the previously documented association with endometriosis (ovarian
      neoplasms) and the prominent endometrial involvement (uterine corpus neoplasms), 
      we believe these are best regarded as of Mullerian origin and representing
      adenocarcinomas which differentiate along mesonephric lines; as such, we propose 
      the term mesonephric-like Mullerian adenocarcinoma.
FAU - Mirkovic, Jelena
AU  - Mirkovic J
AD  - Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
FAU - McFarland, Marie
AU  - McFarland M
AD  - Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern 
      Ireland, UK.
FAU - Garcia, Elizabeth
AU  - Garcia E
AD  - Department of Pathology.
FAU - Sholl, Lynette M
AU  - Sholl LM
AD  - Department of Pathology.
FAU - Lindeman, Neal
AU  - Lindeman N
AD  - Department of Pathology.
FAU - MacConaill, Laura
AU  - MacConaill L
AD  - Department of Pathology.
AD  - Dana-Farber Cancer Institute, Boston, MA.
FAU - Dong, Fei
AU  - Dong F
AD  - Department of Pathology.
FAU - Hirsch, Michelle
AU  - Hirsch M
AD  - Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and
      Women's Hospital.
FAU - Nucci, Marisa R
AU  - Nucci MR
AD  - Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and
      Women's Hospital.
FAU - Quick, Charles M
AU  - Quick CM
AD  - Department of Pathology, University of Arkansas for Medical Sciences, Little
      Rock, AR.
FAU - Crum, Christopher P
AU  - Crum CP
AD  - Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and
      Women's Hospital.
FAU - McCluggage, W Glenn
AU  - McCluggage WG
AD  - Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern 
      Ireland, UK.
FAU - Howitt, Brooke E
AU  - Howitt BE
AD  - Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and
      Women's Hospital.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (KRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Adenocarcinoma/classification/*genetics/pathology
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*genetics
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - DNA Copy Number Variations
MH  - DNA Mutational Analysis/*methods
MH  - Female
MH  - Gene Expression Profiling/*methods
MH  - Genetic Predisposition to Disease
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Middle Aged
MH  - Mullerian Ducts/pathology
MH  - *Mutation
MH  - Mutation Rate
MH  - Ovarian Neoplasms/classification/*genetics/pathology
MH  - Phenotype
MH  - Predictive Value of Tests
MH  - Proto-Oncogene Proteins p21(ras)/*genetics
MH  - Terminology as Topic
MH  - Uterine Neoplasms/classification/*genetics/pathology
MH  - Wolffian Ducts/pathology
EDAT- 2017/10/07 06:00
MHDA- 2019/02/27 06:00
CRDT- 2017/10/07 06:00
PHST- 2017/10/07 06:00 [pubmed]
PHST- 2019/02/27 06:00 [medline]
PHST- 2017/10/07 06:00 [entrez]
AID - 10.1097/PAS.0000000000000958 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2018 Feb;42(2):227-233. doi: 10.1097/PAS.0000000000000958.