title: Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis.
abstract: Pseudomyxoma peritonei (PMP) is a rare abdominal malignancy. We hypothesized that next-generation exomic sequencing would identify recurrent mutations that may have prognostic or therapeutic implications. Ten patients were selected on the basis of availability of tissue and adequate follow-up. They were treated at our institution between September 2002 and August 2004. Using next-generation exomic sequencing, we tested for mutations in 236 cancer-related genes in formalin-fixed paraffin-embedded slides. MCL1 amplification was additionally tested with immunohistochemical staining. Detectable mutations were found in 8 patients (80%). Seven patients harbored a KRAS mutation, most commonly involving codon 12. Four GNAS mutations (R201H/R201C substitutions) were also detected. MCL1 and JUN were concurrently amplified in three patients. One patient with MCL1 and JUN amplification had concurrent amplification of MYC and NFKBIA. ZNF703 was amplified in one patient. Patients with MCL1 amplification were also found to express MCL1 with immunohistochemistry, but MCL1 expression was also detected in some patients without amplification. To our knowledge, we are the first to report MCL1 and JUN coamplification in PMP. Expression of MCL1 may not be completely dependent on amplification. The prognostic and therapeutic implications of these recurrent mutational events are the subject of ongoing investigation.
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Terence T
authors.initials: TT
authors.lastname: Sio
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Mansfield
authors.affiliation: Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Travis E
authors.initials: TE
authors.lastname: Grotz
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Rondell P
authors.initials: RP
authors.lastname: Graham
authors.affiliation: 1] Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA [2] Division of Experimental Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Molina
authors.affiliation: Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Florencia G
authors.initials: FG
authors.lastname: Que
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002864:Chromogranins; D003710:Demography; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015321:Gene Rearrangement / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011553:Pseudomyxoma Peritonei / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics
chemical_list: D002864:Chromogranins; C117307:KRAS protein, human; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins