Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children42210.24287/1726-1708-2020-19-4-82-87ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИPrevalence of FOXO1 gene abnormalities in a group of round-cell rhabdomyosarcomas with alveolar morphologyРаспространенность аномалий гена FOXO1 в группе круглоклеточных рабдомиосарком с альвеолярной морфологиейhttps://orcid.org/0000-0001-5354-7067SharlaiA. S.ШарлайА. С.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-6384-7645BotiralievaG. K.БотиралиеваГ. K.
Uzbekistan

Tashkent

Ташкент

https://orcid.org/0000-0003-1308-8622DruyA. E.ДруйА. Е.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-9375-7517RoshchinV. Yu.РощинВ. Ю.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-7732-8184KonovalovD. M.КоноваловД. М.
Russian Federation

Dmitry M. Konovalov, MD, PhD, head of the Pathology Anatomy Department

1 Samory Mashela St., Moscow 117997

Коновалов Дмитрий Михайлович, канд. мед. наук, заведующий патологоанатомическим отделением

117997, Москва, ул. Саморы Машела, 1 

dmk_nadf@mail.ruDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology Ministry of Healthcare of Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава РоссииIpsum Pathology LLCOOO “Ipsum Pathology”0812202019482872112202021122020Copyright ©; 2025, «D. Rogachev NMRCPHOI»Copyright ©; 2025, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2025«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/422

Rhabdomyosarcomas (RMS) are group of soft tissue malignant tumours predominantly childhood. Alveolar rhabdomyosarcoma (aRMS) is the second most common variant of RMS. The majority of aRMSs display a translocations of FOXO1 gene. Such tumours are aggressive, metastasize early and are associated with a worse prognosis for the patient. However, some aRMS cases are rhabdomyosarcomas without classic chromosomal rearrangements. These tumors also have alveolar morphology, but neoplastic cells lack the FOXO1 gene translocation. Such fusion-negative round-cell RMSs behave clinically differently and have a better prognosis. The aim of the present study was to assess the prevalence of FOXO1 gene rearrangements in the group of round cell rhabdomyosarcomas with alveolar morphology. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study group consisted of 250 formalin-fixed paraffin-embedded samples from patients with RMS. The cytogenetic study was performed by fluorescence in situ hybridization with a locus-specific identifier (LSI) for FOXO1 (13q14). The PAX3-FOXO1 (COSF247) and PAX7-FOXO1 (COSF287) fusion transcripts was detected by RT-PCR. In the study group 1 (аRMS), the rearrangement of PAX3/7-FOXO1 was detected in 44% of cases, in 32% of cases was detected a combined rearrangement with amplification of the 3' FOXO1. In one case, the amplification of the 3' end of the FOXO1 gene was detected without rearrangement; this sample was sent for additional PCR study, as a result of which the chimeric PAX3-FOXO1 transcript was detected. In 22% cases cytogenetic abnormalities were not found. has not been identified. In group 2 (embryonal RMS) we did not detect translocation. The group of round-cell PMCs is heterogeneous and is represented by three variants of genetic events that determine the disease prognosis. At the same time, FOXO1 gene abnormalities are not found in the RMS group with non-alveolar morphology.

Рабдомиосаркомы (РМС) – группа злокачественных опухолей мягких тканей, как считалось, преимущественно детского возраста. Альвеолярная РМС (аРМС) является вторым по частоте встречаемости вариантом РМС. В подавляющем большинстве случаев при аРМС обнаруживается транслокация гена FOXO1. Такие опухоли агрессивны, рано метастазируют и ассоциированы с худшим прогнозом для пациента. Однако часть случаев аРМС относятся к РМС без классических хромосомных перестроек. Данные опухоли также имеют альвеолярную морфологию, но в неопластических клетках отсутствует транслокация гена FOXO1. Эти неперестроенные круглоклеточные РМС клинически ведут себя иначе и имеют более благоприятный прогноз. Цель работы: провести оценку частоты встречаемости перестроек гена FOXO1 в группе круглоклеточных РМС с альвеолярной морфологией. Исследуемую группу составили 250 образцов опухолевой ткани пациентов с РМС. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. Цитогенетическое исследование проводилось методом флуоресцентной гибридизации in situ с локус-специфичным зондом FOXO1 (13q14). Выявление химерных транскриптов PAX3-FOXO1 (COSF247) и PAX7-FOXO1 (COSF287) проводилось с помощью полимеразной цепной реакции (ПЦР) в режиме реального времени. В исследуемой группе 1 (аРМС) перестройка PAX3/7-FOXO1 была выявлена в 44% случаев, в 32% была обнаружена сочетанная перестройка с амплификацией 3’ конца гена FOXO1. В 1 случае выявлена амплификация 3’ конца гена FOXO1 без перестройки, данный образец был отправлен на дополнительное исследование методом ПЦР, в результате которого был обнаружен химерный транскрипт PAX3-FOXO1. В 22% случаев не было выявлено никаких изменений. В группе 2 (эмбриональные РМС) в 100% случаев не было выявлено перестройки гена FOXO1. Группа круглоклеточных РМС с генетической точки зрения является неоднородной и представлена 3 вариантами генетических событий, определяющих прогноз течения болезни. В то же время в группе РМС с неальвеолярной морфологией аномалии гена FOXO1 не встречаются.

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