Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer

Shimada, Yasuhiro; Yagi, Ryoma; Kameyama, Hitoshi; Nagahashi, Masayuki; Ichikawa, Hiroshi; Tajima, Yosuke; Okamura, Takuma; Nakano, Masaaki; Sato, Yo; Matsuzawa, T.; Sakata, Jun; Kobayashi, Takashi; Nogami, Hitoshi; Maruyama, Satoshi; Takii, Yasumasa; Kawasaki, Takashi; Homma, Kei ichi; Izutsu, Hiroshi; Kodama, Kazuhisa; Ring, Jennifer E.; Protopopov, Alexei; Lyle, Stephen; Okuda, Shujiro; Akazawa, Kohei; Wakai, Toshifumi

doi:10.1016/j.humpath.2017.02.004

Cited by 32 publications

(24 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously described (15,(31)(32)(33)(34), formalin-fixed, paraffinembedded (FFPE) samples were used for next-generation sequencing (NGS), and genetic alterations, including RNF43, were evaluated. Briefly, hematoxylin and eosin-stained sections were used to assess tumor content, to ensure that >50% tumor content was present.…”

Section: Comprehensive Genomic Sequence Analysis Of Primary Tumorsmentioning

confidence: 99%

RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

Right-sided colorectal cancer (RCRC) demonstrates worse survival outcome compared with left-sided CRC (LCRC). Recently, the importance of RNF43 mutation and BRAF V600E mutation has been reported in the serrated neoplasia pathway, which is one of the precancerous lesions in RCRC. It was hypothesized that the clinical significance of RNF43 mutation differs according to primary tumor sidedness. To test this hypothesis, the clinicopathological characteristics and survival outcome of patients with RNF43 mutation in RCRC and LCRC were investigated. Stage I-IV CRC patients (n=201) were analyzed. Genetic alterations including RNF43 using a 415-gene panel were investigated. Clinicopathological characteristics between RNF43 wild-type and RNF43 mutanttype were analyzed. Moreover, RNF43 mutant-type was classified according to primary tumor sidedness, i.e., rightsided RNF43 mutant-type or left-sided RNF43 mutant-type, and the clinicopathological characteristics between the two groups were compared. RNF43 mutational prevalence, spectrum and frequency between our cohort and TCGA samples were compared. RNF43 mutation was observed in 27 out of 201 patients (13%). Multivariate analysis revealed that age (≥65), absence of venous invasion, and BRAF V600E mutation were independently associated with RNF43 mutation. Among the 27 patients with RNF43 mutation, 12 patients were right-sided RNF43 mutant-type and 15 left-sided RNF43 mutant-type. Right-sided RNF43 mutant-type was significantly associated with histopathological grade 3, presence of lymphatic invasion, APC wild, BRAF V600E mutation, microsatellite instability-high (MSI-H), and RNF43 nonsense/ frameshift mutation compared with left-sided RNF43 mutanttype. Similarly, RNF43 nonsense/frameshift mutations were more frequently observed in RCRC compared with LCRC in the TCGA cohort (P=0.042). Right-sided RNF43 mutant-type exhibited significantly worse overall survival than RNF43 wild-type and left-sided RNF43 mutant-type (P=0.001 and P=0.023, respectively) in stage IV disease. RNF43 mutation may be a distinct molecular subtype which is associated with aggressive tumor biology along with BRAF V600E mutation in RCRC.

show abstract

Section: Comprehensive Genomic Sequence Analysis Of Primary Tumorsmentioning

confidence: 99%

RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In our study, DNA with a Q-ratio (129 bp/41 bp) > 0.1 was designated as being of high enough quality for NGS analysis based on our previous results. 14, 19 …”

Section: Methodsmentioning

confidence: 99%

Formalin-fixed paraffin-embedded sample conditions for deep next generation sequencing

Nagahashi

Shimada

Ichikawa

et al. 2017

Journal of Surgical Research

Self Cite

View full text Add to dashboard Cite

Introduction Precision medicine is only possible in oncology practice if targetable genes in fragmented DNA, such as DNA from formalin-fixed paraffin-embedded (FFPE) samples, can be sequenced using next generation sequencing (NGS). The aim of this study is to examine the quality and quantity of DNA from FFPE cancerous tissue samples from surgically resected and biopsy specimens. Methods DNA was extracted from unstained FFPE tissue sections prepared from surgically resected specimens of breast, colorectal and gastric cancer, and biopsy specimens of breast cancer. A total quantity of DNA ≥60 ng from a sample was considered adequate for NGS. The DNA quality was assessed by Q-ratios, with a Q-ratio >0.1 considered sufficient for NGS. Results The Q-ratio for DNA from FFPE tissue processed with neutral-buffered formalin was significantly better than that processed with unbuffered formalin. All Q-ratios for DNA from breast, colorectal and gastric cancer samples indicated DNA levels sufficient for NGS. DNA extracted from gastric cancer FFPE samples prepared within the last seven years is suitable for NGS analysis, whereas those older than seven years may not be suitable. Our data suggested that adequate amounts of DNA can be extracted from FFPE samples, not only of surgically resected tissue but also of biopsy specimens. Conclusion The type of formalin used for fixation and the time since FFPE sample preparation affect DNA quality. Sufficient amounts of DNA can be extracted from FFPE samples of both surgically resected and biopsy tissue, thus expanding the potential diagnostic uses of NGS in a clinical setting.

show abstract

“…Next generation sequencing‐based gene panel testing enables detection of HER2 gene amplification. We have examined HER2 overexpression and amplification by IHC, FISH, and gene panel tests in colorectal cancer patients, and reported that gene panel testing has the same utility as IHC and FISH for detecting HER2‐positive patients that are candidates for HER2‐targeted therapy . Recently, it has also been revealed that the majority of HER2 somatic mutations without HER2 gene amplification in breast cancer patients are activating mutations, which can be targeted by anti‐HER2 therapies .…”

Section: Target Genes or Resistance‐related Genes For Molecular‐targementioning

confidence: 99%

“…In addition to lung adenocarcinoma, another successful example of a treatment strategy involving precision medicine is anti-human epidermal growth factor receptor 2 (HER2) therapy using trastuzumab and other molecular- are candidates for HER2-targeted therapy. 12 Recently, it has also been revealed that the majority of HER2 somatic mutations without HER2 gene amplification in breast cancer patients are activating mutations, which can be targeted by anti-HER2 therapies. 41 Next generation sequencing-based gene panel testing will identify patients with breast or other solid cancers with the HER2 activating mutations, who will potentially benefit from anti-HER2 therapies.…”

Section: Targ E T G Ene S or Re S Is Tan Ce-rel Ated G Ene S For Momentioning

confidence: 99%

“…It is therefore important to consider geographic and ethnic differences when looking to understand the profile of genomic alterations, and apply NGS analysis to the development of therapies for Asian patients. Recently, we studied several types of solid cancers, including colorectal, gastric, lung, and breast cancer, in Japan utilizing NGS-based comprehensive genomic panel testing, 8,[11][12][13][14][15][16][17][18] and revealed some differences in genomic alterations between Asian and non-Asian populations.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Next generation sequencing‐based gene panel tests for the management of solid tumors

et al. 2018

Self Cite

View full text Add to dashboard Cite

Next generation sequencing (NGS) has been an invaluable tool to put genomic sequencing into clinical practice. The incorporation of clinically relevant target sequences into NGS‐based gene panel tests has generated practical diagnostic tools that enable individualized cancer‐patient care. The clinical utility of gene panel testing includes investigation of the genetic basis for an individual's response to therapy, such as signaling pathways associated with a response to specific therapies, microsatellite instability and a hypermutated phenotype, and deficiency in the DNA double‐strand break repair pathway. In this review, we describe the concept of precision cancer medicine using target sequences in gene panel tests as well as the importance of the control of sample quality in routine NGS‐based genomic testing. We describe geographic and ethnic differences in cancer genomes, and discuss issues that need to be addressed in the future based on our experiences in Japan.

show abstract

Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer

Cited by 32 publications

References 29 publications

RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer

RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer

Formalin-fixed paraffin-embedded sample conditions for deep next generation sequencing

Next generation sequencing‐based gene panel tests for the management of solid tumors

Contact Info

Product

Resources

About