title: Next-Generation Sequencing of Matched Primary and Metastatic Rectal Adenocarcinomas Demonstrates Minimal Mutation Gain and Concordance to Colonic Adenocarcinomas.
abstract: BACKGROUND
  -Colorectal carcinoma is the third most common cause of cancer death in males and females in the United States. Rectal adenocarcinoma can have distinct therapeutic and surgical management from colonic adenocarcinoma owing to its location and anatomic considerations.
  
  
  OBJECTIVE
  -To determine the oncologic driver mutations and better understand the molecular pathogenesis of rectal adenocarcinoma in relation to colon adenocarcinoma.
  
  
  METHODS
  -Next-generation sequencing was performed on 20 cases of primary rectal adenocarcinoma with a paired lymph node or solid organ metastasis by using an amplicon-based assay of more than 2800 Catalogue of Somatic Mutations in Cancer (COSMIC)-identified somatic mutations.
  
  
  RESULTS
  -Next-generation sequencing data were obtained on both the primary tumor and metastasis from 16 patients. Most rectal adenocarcinoma cases demonstrated identical mutations in the primary tumor and metastasis (13 of 16, 81%). The mutations identified, listed in order of frequency, included TP53, KRAS, APC, FBXW7, GNAS, FGFR3, BRAF, NRAS, PIK3CA, and SMAD4.
  
  
  CONCLUSIONS
  -The somatic mutations identified in our rectal adenocarcinoma cohort showed a strong correlation to those previously characterized in colonic adenocarcinoma. In addition, most rectal adenocarcinomas harbored identical somatic mutations in both the primary tumor and metastasis. These findings demonstrate evidence that rectal adenocarcinoma follows a similar molecular pathogenesis as colonic adenocarcinoma and that sampling either the primary or metastatic lesion is valid for initial evaluation of somatic mutations and selection of possible targeted therapy.
authors.affiliation: From the Departments of Pathology and Genomic Medicine (Drs Crumley, Olsen, Schwartz, and Portier and Ms Pepper) and Oncology (Dr Phan), Houston Methodist Hospital, Houston, Texas.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Crumley
authors.affiliation: From the Departments of Pathology and Genomic Medicine (Drs Crumley, Olsen, Schwartz, and Portier and Ms Pepper) and Oncology (Dr Phan), Houston Methodist Hospital, Houston, Texas.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Pepper
authors.affiliation: From the Departments of Pathology and Genomic Medicine (Drs Crumley, Olsen, Schwartz, and Portier and Ms Pepper) and Oncology (Dr Phan), Houston Methodist Hospital, Houston, Texas.
authors.forename: Alexandria T
authors.initials: AT
authors.lastname: Phan
authors.affiliation: From the Departments of Pathology and Genomic Medicine (Drs Crumley, Olsen, Schwartz, and Portier and Ms Pepper) and Oncology (Dr Phan), Houston Methodist Hospital, Houston, Texas.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Olsen
authors.affiliation: From the Departments of Pathology and Genomic Medicine (Drs Crumley, Olsen, Schwartz, and Portier and Ms Pepper) and Oncology (Dr Phan), Houston Methodist Hospital, Houston, Texas.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Schwartz
authors.affiliation: From the Departments of Pathology and Genomic Medicine (Drs Crumley, Olsen, Schwartz, and Portier and Ms Pepper) and Oncology (Dr Phan), Houston Methodist Hospital, Houston, Texas.
authors.forename: Bryce P
authors.initials: BP
authors.lastname: Portier
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002864:Chromogranins / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D044783:F-Box Proteins / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology; D051901:Smad4 Protein / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D018797:Cell Cycle Proteins; D002864:Chromogranins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C117307:KRAS protein, human; D008565:Membrane Proteins; D051901:Smad4 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C406732:GNAS protein, human; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras)