Multi-regional sequencing reveals clonal and polyclonal seeding from primary tumor to metastases in advanced gastric cancer View Full Text


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Article Info

DATE

2020-01-07

AUTHORS

Yosuke Hirotsu, Masao Hada, Kenji Amemiya, Toshio Oyama, Hitoshi Mochizuki, Masao Omata

ABSTRACT

BackgroundTumor metastases to lymph nodes and distant organs are associated with worse prognosis in gastric cancer. However, little is known about the genetic profiles, subclonal architecture, and evolutional processes across primary tumors and metastases.MethodsWe analyzed the genetic alterations of 106 multiregional samples including primary tumors, lymph node metastases, and visceral metastases from 10 patients with advanced gastric cancer. Histologically different portions were obtained by laser-capture microdissection. We reconstructed the subclonal architectures and inferred the primary to lymph or visceral metastatic seeding patterns.ResultsThe different histological portions in primary tumors had common mutations, suggesting common ancestral tumor origins transformed into distinct histological types. In almost all cases, TP53 mutations were identified as clonal mutations across primary tumors and metastases. Subclonal reconstruction and phylogenetic analysis showed primary tumors were classified into monoclonal or polyclonal tumors. All monoclonal primary tumors disseminated as metastases with the same tumor composition (100%, 26/26 samples). In contrast, polyclonal primary tumors mainly spread as metastases by way of polyclonal seeding (84%: 37/44 samples).ConclusionsClonal mutations were maintained at both the primary and metastatic sites and genetic divergence of these was low. These findings shed light on the genetic basis of primary tumor dissemination and metastatic processes in advanced gastric cancer. More... »

PAGES

553-564

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    http://scigraph.springernature.com/pub.10.1007/s00535-019-01659-6

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    http://dx.doi.org/10.1007/s00535-019-01659-6

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31912238


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    35 schema:description BackgroundTumor metastases to lymph nodes and distant organs are associated with worse prognosis in gastric cancer. However, little is known about the genetic profiles, subclonal architecture, and evolutional processes across primary tumors and metastases.MethodsWe analyzed the genetic alterations of 106 multiregional samples including primary tumors, lymph node metastases, and visceral metastases from 10 patients with advanced gastric cancer. Histologically different portions were obtained by laser-capture microdissection. We reconstructed the subclonal architectures and inferred the primary to lymph or visceral metastatic seeding patterns.ResultsThe different histological portions in primary tumors had common mutations, suggesting common ancestral tumor origins transformed into distinct histological types. In almost all cases, TP53 mutations were identified as clonal mutations across primary tumors and metastases. Subclonal reconstruction and phylogenetic analysis showed primary tumors were classified into monoclonal or polyclonal tumors. All monoclonal primary tumors disseminated as metastases with the same tumor composition (100%, 26/26 samples). In contrast, polyclonal primary tumors mainly spread as metastases by way of polyclonal seeding (84%: 37/44 samples).ConclusionsClonal mutations were maintained at both the primary and metastatic sites and genetic divergence of these was low. These findings shed light on the genetic basis of primary tumor dissemination and metastatic processes in advanced gastric cancer.
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    42 schema:keywords BackgroundTumor metastasis
    43 ConclusionsClonal mutations
    44 MethodsWe
    45 Multi-regional sequencing
    46 TP53 mutations
    47 advanced gastric cancer
    48 alterations
    49 analysis
    50 ancestral tumor origins
    51 architecture
    52 basis
    53 cancer
    54 cases
    55 clonal mutations
    56 common ancestral tumor origins
    57 common mutations
    58 composition
    59 contrast
    60 different histological portions
    61 different portions
    62 dissemination
    63 distant organs
    64 distinct histological types
    65 divergence
    66 evolutional process
    67 findings
    68 gastric cancer
    69 genetic alterations
    70 genetic basis
    71 genetic divergence
    72 genetic profile
    73 histological portions
    74 histological type
    75 laser capture microdissection
    76 light
    77 lymph
    78 lymph node metastasis
    79 metastasis
    80 metastatic process
    81 metastatic seeding patterns
    82 metastatic sites
    83 microdissection
    84 monoclonal primary tumors
    85 multiregional samples
    86 mutations
    87 node metastasis
    88 nodes
    89 organs
    90 origin
    91 patients
    92 patterns
    93 phylogenetic analysis
    94 polyclonal primary tumors
    95 polyclonal seeding
    96 polyclonal tumors
    97 portion
    98 primary
    99 primary tumor
    100 primary tumor dissemination
    101 process
    102 profile
    103 prognosis
    104 reconstruction
    105 same tumor composition
    106 samples
    107 seeding
    108 seeding patterns
    109 sequencing
    110 sites
    111 subclonal architecture
    112 subclonal reconstruction
    113 tumor composition
    114 tumor dissemination
    115 tumor origin
    116 tumors
    117 types
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    122 schema:name Multi-regional sequencing reveals clonal and polyclonal seeding from primary tumor to metastases in advanced gastric cancer
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