title: Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer.
abstract: HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 IHC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P < .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment.
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan. Electronic address: shimaday@med.niigata-u.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Yagi
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kameyama
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagahashi
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tajima
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Mae
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata 949-7302, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata 949-7302, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Matsuzawa
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sakata
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Surgery, Niigata Cancer Center Hospital, Niigata 951-8566, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nogami
authors.affiliation: Department of Surgery, Niigata Cancer Center Hospital, Niigata 951-8566, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Department of Surgery, Niigata Cancer Center Hospital, Niigata 951-8566, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Takii
authors.affiliation: Department of Pathology, Niigata Cancer Center Hospital, Niigata 951-8566, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Department of Pathology, Niigata Cancer Center Hospital, Niigata 951-8566, Japan.
authors.forename: Kei-Ichi
authors.initials: KI
authors.lastname: Homma
authors.affiliation: Diagnostics Research Department, Life innovation Research Institute, Denka Innovation Center, Denka Co, Ltd, Tokyo 194-8560, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Izutsu
authors.affiliation: Diagnostics Research Department, Life innovation Research Institute, Denka Innovation Center, Denka Co, Ltd, Tokyo 194-8560, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kodama
authors.affiliation: KEW, Inc., Cambridge, MA 02139, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ring
authors.affiliation: KEW, Inc., Cambridge, MA 02139, USA.
authors.forename: Alexei
authors.initials: A
authors.lastname: Protopopov
authors.affiliation: KEW, Inc., Cambridge, MA 02139, USA; University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lyle
authors.affiliation: Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Shujiro
authors.initials: S
authors.lastname: Okuda
authors.affiliation: Department of Medical Informatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
chemical_list: D014408:Biomarkers, Tumor; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; C117307:KRAS protein, human; C508053:ERBB2 protein, human
keywords: Colorectal cancer; Comprehensive genomic sequencing; Fluorescence in situ hybridization; HER2; Immunohistochemistry; Next-generation sequencing