International journal of clinical oncology · 2026
Paired tumor-normal targeted sequencing supports clonal independence of multiple primary malignancies in patients with gastrointestinal stromal tumors.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Asakawa Yukiko, Hirotsu Yosuke, Omata Masao
Аннотация
BACKGROUND: The association between gastrointestinal stromal tumors (GIST) and multiple primary malignancies (MPM) is recognized, but its molecular basis has not been investigated.
METHODS: The institutional registry recorded 26,783 patients diagnosed between October 2006 and December 2020, of whom 69 had GIST. Of these, 33 consented to genetic analysis under a prospective biospecimen-collection program. We compared clinicopathological characteristics between patients with and those without MPM. We performed paired tumor-normal targeted sequencing using an amplicon-based panel on GIST and MPM tissue from 18 patients, with matched peripheral blood as the germline reference.
RESULTS: MPM occurred in 19 of 69 GIST patients (27.5%), ranking fourth among eight cancer types, after gastric (31.5%), colorectal (29.8%) and esophageal cancer (28.4%) in our institutional registry. Older age was the only factor significantly associated with MPM (median 77.0 vs. 65.0 years; p = 0.007). Among the 33 patients who consented to genetic analysis, 19 had MPM and 18 were evaluable for paired tumor-normal sequencing. GISTs harbored KIT or PDGFRA mutations, whereas MPMs carried tumor type-specific driver alterations including TP53, APC, KRAS and PIK3CA. No shared somatic variants were detected within the limits of the targeted sequencing panel, supporting clonal independence between GIST and co-occurring malignancies irrespective of temporal classification.
CONCLUSION: MPM frequently occur in patients with GIST and arise independently. Paired tumor-normal sequencing supports clonal independence between GIST and co-occurring malignancies in all evaluable cases, regardless of timing. Age-appropriate cancer screening and careful evaluation for gastrointestinal malignancies may be considered, particularly in older patients with GIST.
METHODS: The institutional registry recorded 26,783 patients diagnosed between October 2006 and December 2020, of whom 69 had GIST. Of these, 33 consented to genetic analysis under a prospective biospecimen-collection program. We compared clinicopathological characteristics between patients with and those without MPM. We performed paired tumor-normal targeted sequencing using an amplicon-based panel on GIST and MPM tissue from 18 patients, with matched peripheral blood as the germline reference.
RESULTS: MPM occurred in 19 of 69 GIST patients (27.5%), ranking fourth among eight cancer types, after gastric (31.5%), colorectal (29.8%) and esophageal cancer (28.4%) in our institutional registry. Older age was the only factor significantly associated with MPM (median 77.0 vs. 65.0 years; p = 0.007). Among the 33 patients who consented to genetic analysis, 19 had MPM and 18 were evaluable for paired tumor-normal sequencing. GISTs harbored KIT or PDGFRA mutations, whereas MPMs carried tumor type-specific driver alterations including TP53, APC, KRAS and PIK3CA. No shared somatic variants were detected within the limits of the targeted sequencing panel, supporting clonal independence between GIST and co-occurring malignancies irrespective of temporal classification.
CONCLUSION: MPM frequently occur in patients with GIST and arise independently. Paired tumor-normal sequencing supports clonal independence between GIST and co-occurring malignancies in all evaluable cases, regardless of timing. Age-appropriate cancer screening and careful evaluation for gastrointestinal malignancies may be considered, particularly in older patients with GIST.