研究者詳細 - 真里谷　奨

論文 - 真里谷　奨

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Large number of CD68+/CD163+ Hofbauer cells and characteristic vascular structural alterations in the placental villi of cases with placenta accreta spectrum.

Hazuki Kashiwagi, Kengo Shigehara, Terufumi Kubo, Yoshihiko Hirohashi, Tasuku Mariya, Kazuhiko Matsuo, Tomoyuki Minowa, Shin-Ichi Ishioka, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Tadashi Hasegawa, Tsuyoshi Saito, Toshihiko Torigoe

Medical molecular morphology 2025年03月 [国内誌]

Placenta accreta spectrum (PAS) is a serious disease leading to complications and maternal death. The objective of the study was to characterize the placental villi and blood vessels of PAS villi histopathologically. We investigated 10 cases of PAS (five cases of placenta increta, two cases of placenta accreta, and three cases of placenta percreta) histologically. Immunohistochemical staining using anti-CD68 or anti-CD163 antibodies was performed to detect and count Hofbauer cells. Immunohistochemical staining with an anti-CD34 antibody was used to detect vascular endothelial cells, and the number and area of vessels were analyzed. The numbers of CD68-positive or CD163-positive Hofbauer cells were larger in PAS cases compared with control cases. The vascular area in villi was smaller in PAS cases compared with control cases. The number of blood vessels in villi was slightly higher in PAS cases than in control cases. The numbers of Hofbauer cells and vessels in villi were larger in PAS cases compared with control cases, whereas the area of vessels in villi was smaller in PAS cases compared with control cases. Although their biological meaning is elusive, these findings provide novel insights into the pathogenesis of PAS, particularly regarding the role of Hofbauer cells in immune-suppressive role and angiogenesis and the alterations in vascular structure and hemodynamics in the chorionic villi.

Identification and Phenotypic Characterization of Neoantigen-Specific Cytotoxic CD4+ T Cells in Endometrial Cancer

Minami Fusagawa, Serina Tokita, Kenji Murata, Tasuku Mariya, Mina Umemoto, Shintaro Sugita, Kazuhiko Matsuo, Yoshihiko Hirohashi, Tsuyoshi Saito, Takayuki Kanaseki, Toshihiko Torigoe

Cancer Immunology Research 2025年02月

Maternal age and the rising incidence of hypertensive disorders of pregnancy: A comprehensive analysis of national claims data from Japan.

Naomi Maeda, Masayuki Koyama, Shintaro Takatsuka, Keisuke Oyatani, Nobuaki Himuro, Tasuku Mariya, Yoshika Kuno, Shiro Hinotsu, Tsuyoshi Saito, Hirofumi Ohnishi

PloS one 20 ( 2 ) e0319177 2025年 [国際誌]

BACKGROUND: Hypertensive disorders of pregnancy (HDP) significantly increase the risk of developing hypertension and cardiovascular disease (CVD) later in life and are a major cause of maternal mortality. However, little is known about the nationwide, long-term, all-inclusive status of HDP. OBJECTIVE: To estimate the incidence of HDP from 2011 to 2019 in Hokkaido, Japan, with a focus on age groups. METHODS: Using National Database (NDB) insurance medical data, a retrospective analysis was conducted. Due to the absence of direct pregnancy data, birth numbers were used as a surrogate for the number of pregnant women to calculate the incidence of HDP. RESULTS: The average incidence rate of HDP over 9 years was 6.37%. The incidence rate was lowest among women aged 25-29 years, at 5.58% (95% confidence interval [CI]: 5.43-5.73), and increased with age, peaking at 10.58% (95% CI: 10.10-11.09) among women over 40 years. Notably, the incidence rate for women under 20 years of age was 6.70% (95% CI: 5.97-7.51), which was higher than that for women in their 20s. A mean annual increase of 0.25% in age-adjusted incidence was observed during this period, which was statistically significant (R² = 0.87, p < 0.01). CONCLUSION: This study reveals that the risk of developing HDP is associated with both older childbearing and younger pregnancies and follows a J-curve, suggesting that factors other than maternal aging also contribute to the increased incidence of HDP and that further research on risk factors for HDP, which is on the rise worldwide, is urgently needed.

遺伝子関連検査を知る近年のPGT-Mの検査法について

真里谷奨

遺伝子医学 ( (株)メディカルドゥ ) 14 ( 4 ) 101 - 106 2024年12月

PGT-M(preimplantation genetic testing for monogenic/single-gene defects)に用いる胚の生検検体は5～10細胞とごくわずかであり,全ゲノム増幅を経る必要があるため特有の検査上のピットフォールが存在する。そのため,個々の単一遺伝子疾患の確実な検査系の構築はテーラーメイドかつ複雑であるが,ロングリードシーケンサー等の新たなツールの活用により,複雑な構造異常を伴うバリアントやde noveの発端者など,多様な症例にも対応可能となっている。(著者抄録)

Impact of colposcopy-guided carbon dioxide laser vaporization therapy on peripheral cervical intraepithelial neoplasia lesions.

Tasuku Mariya, Akira Nishikawa, Mina Umemoto, Shiori Ogawa, Tsuyoshi Saito

Taiwanese journal of obstetrics & gynecology 63 ( 6 ) 846 - 852 2024年11月 [国際誌]

OBJECTIVE: Laser vaporization is less invasive than conization for cervical intraepithelial neoplasia (CIN). The outcome of laser vaporization for CIN is empirically known to depend on the colposcopic findings, especially localization of the lesion. In this study, we sought to identify factors involved in the outcome of laser vaporization. MATERIALS AND METHODS: We retrospectively investigated 290 cases of CIN (CIN2, n = 180; CIN3, n = 110) treated with laser evaporation at Nishikawa Women's Health Clinic between 2018 and 2021. All treatments were performed using a carbon dioxide laser under either colposcopic vision (n = 172) or direct vision using a vaginal speculum (n = 118). Risk factors were statistically examined for cure rate after treatment. RESULTS: Multivariate analysis using a logistic regression model identified independent factors affecting the success of treatment to be high-risk human papillomavirus infection status preoperatively, CIN grade, presence of CIN lesions at the periphery of the cervix, and the surgical method used. Colposcopy-guided laser vaporization reduced the risk of treatment failure by 84% (odds ratio 0.16, 95% confidence interval 0.06-0.46; p = 0.001) compared with direct vision using a vaginal speculum. For lesions at the periphery of the cervix, most of the treatment failures were in the group that was not guided by colposcopy (p = 0.031). CONCLUSION: The presence of a peripheral CIN lesion was suggested to be a risk factor for treatment failure. Laser vaporization under colposcopic vision is recommended for treatment of peripheral CIN lesions.

【遺伝学的検査Up to Date】遺伝学的検査の応用法を知ろう! 着床前診断を知ろう!

真里谷奨, 倉橋浩樹

小児科診療 ( (株)診断と治療社 ) 87 ( 11 ) 1579 - 1584 2024年11月

＜文献概要＞▽網羅的染色体解析による検査手法の確立により,着床前診断(preimplantation genetic testing:PGT)の診断精度は大きく向上した.▽PGTにまつわる倫理的な議論,特にPGT-M(重篤な遺伝性疾患を対象とした着床前遺伝学的検査)に関連した内容は継続して行われており,検査適応については症例ごとの詳細な検討が必要となる.▽PGTに関連した技術は現在も進歩を続けており,検査の応用範囲は今後さらに拡大していく可能性が高い.

Successful Outcome of Stage IB3 Cervical Cancer Treated With Neoadjuvant Chemotherapy Followed by Vaginal Radical Trachelectomy: A Case Report.

Masato Tamate, Motoki Matsuura, Masayuki Someya, Tasuku Mariya, Shinichi Ishioka, Tsuyoshi Saito

Cureus 16 ( 10 ) e71626 2024年10月 [国際誌]

Vaginal trachelectomy, which involves resecting the cervix and its parametrium, is a fertility-sparing option for the treatment of early-stage cervical cancer. Although no consensus has been reached on whether simple or radical trachelectomy is preferable, the vaginal approach is typically avoided for tumors larger than 2 cm due to concerns about recurrence. However, some evidence suggests that fertility preservation may still be viable for select patients with larger tumors. This case report describes a woman with bulky cervical cancer who wished to preserve her fertility. After undergoing neoadjuvant chemotherapy (NAC) and vaginal radical trachelectomy (VRT), she achieved a favorable oncological and perinatal outcome, successfully giving birth to a near-full-term baby. The report outlines the patient's management before, during, and after the procedure, including perinatal care. While careful selection of candidates is crucial, accumulating case reports and future trials are expected to shed more light on this treatment approach.

Identification of immunogenic HLA class I and II neoantigens using surrogate immunopeptidomes.

Serina Tokita, Minami Fusagawa, Satoru Matsumoto, Tasuku Mariya, Mina Umemoto, Yoshihiko Hirohashi, Fumitake Hata, Tsuyoshi Saito, Takayuki Kanaseki, Toshihiko Torigoe

Science advances 10 ( 38 ) eado6491 2024年09月 [国際誌]

Neoantigens arising from somatic mutations are tumor specific and induce antitumor host T cell responses. However, their sequences are individual specific and need to be identified for each patient for therapeutic applications. Here, we present a proteogenomic approach for neoantigen identification, named Neoantigen Selection using a Surrogate Immunopeptidome (NESSIE). This approach uses an autologous wild-type immunopeptidome as a surrogate for the tumor immunopeptidome and allows human leukocyte antigen (HLA)-agnostic identification of both HLA class I (HLA-I) and HLA class II (HLA-II) neoantigens. We demonstrate the direct identification of highly immunogenic HLA-I and HLA-II neoantigens using NESSIE in patients with colorectal cancer and endometrial cancer. Fresh or frozen tumor samples are not required for analysis, making it applicable to many patients in clinical settings. We also demonstrate tumor prevention by vaccination with selected neoantigens in a preclinical mouse model. This approach may benefit personalized T cell-mediated immunotherapies.

Microbiological investigation of pregnancies following vaginal radical trachelectomy using 16S rRNA sequencing of FFPE placental specimens.

Risa Tsunematsu, Tasuku Mariya, Mina Umemoto, Shiori Ogawa, Wataru Arai, Suguru E Tanaka, Kyota Ashikawa, Terufumi Kubo, Yoshiyuki Sakuraba, Tsuyoshi Baba, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Saito

FEBS open bio 2024年09月 [国際誌]

This study examined the risk of intrauterine infection associated with radical trachelectomy (RT) in early-stage cervical cancer patients. This procedure preserves fertility but is linked to increased risk of intrauterine infection due to cervical defects during pregnancy. DNA was extracted from the formalin-fixed paraffin-embedded (FFPE) placental specimens of 23 pregnant post-RT patients and 16S rRNA gene sequencing was used for bacterial identification. The prevalence of Lactobacillus crispatus and Burkholderia stabilis was significantly higher in the non-chorioamnionitis group. In contrast, alpha diversity analysis using the PD index showed significantly higher diversity in the chorioamnionitis group (P = 0.04). The demonstrated relationship between chorioamnionitis and microbial diversity affirms the importance of controlling the genital bacterial flora in pregnancies following RT.

Prediction of Mismatch Repair Status in Endometrial Cancer from Histological Slide Images Using Various Deep Learning-Based Algorithms.

Mina Umemoto, Tasuku Mariya, Yuta Nambu, Mai Nagata, Toshihiro Horimai, Shintaro Sugita, Takayuki Kanaseki, Yuka Takenaka, Shota Shinkai, Motoki Matsuura, Masahiro Iwasaki, Yoshihiko Hirohashi, Tadashi Hasegawa, Toshihiko Torigoe, Yuichi Fujino, Tsuyoshi Saito

Cancers 16 ( 10 ) 2024年05月 [国際誌]

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly for gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

Placenta Percreta Progression to Resistance Against Uterine Artery Embolization and Penetration Into the Bladder.

Yukiko Miyashita, Tasuku Mariya, Masayuki Someya, Shinichi Ishioka, Tsuyoshi Saito

Cureus 16 ( 3 ) e55651 2024年03月 [国際誌]

A 31-year-old female sought termination of pregnancy due to a fetal body stalk anomaly diagnosed at 18 weeks of gestation. Despite an anterior placenta previa, successful vaginal delivery occurred. However, placental adhesion over a previous cesarean scar occurred, and part of the placenta could not be removed. Immediate postpartum bleeding prompted imaging studies, revealing extravasation from adherent placental remnants. Uterine artery embolization (UAE) provided initial hemostasis, but recurrent bleeding necessitated re-embolization. Although conservative treatment was initially pursued, significant hematuria prompted reevaluation, revealing extensive uterine wall and bladder penetration. Surgical intervention with total hysterectomy and partial bladder resection was performed, leading to the successful recovery of bladder function following surgical repair. While this case achieved a positive outcome, there is a potential for permanent urinary dysfunction if lesions are more extensive. While achieving a conservative cure is ideal, it is essential to assess the timing for opting for surgical intervention.

The frequency and pathogenicity of BRCA1 and BRCA2 variants in the general Japanese population.

Masashi Idogawa, Tasuku Mariya, Yumi Tanaka, Tsuyoshi Saito, Hiroshi Nakase, Takashi Tokino, Akihiro Sakurai

Journal of human genetics ( (一社)日本癌学会 ) 83回 J - 1048 2024年02月 [国際誌]

Hereditary breast and ovarian cancer syndrome (HBOC) resulting from pathogenic variants of BRCA1 or BRCA2 is the most common and well-documented hereditary tumor. Although founder variants have been identified in population-based surveys in various countries, the types of variants are not uniform across races and regions. Recently, the Tohoku Medical Megabank Organization (ToMMo) released whole-genome sequence data including approximately 54,000 individuals from the general population of the Tohoku area in Japan. We analyzed these data and comprehensively identified the prevalence of BRCA1/2 pathogenic and truncating variants. We believe that an accurate understanding of the unique distribution and characteristics of pathogenic BRCA1/2 variants in Japan through this analysis will enable better surveillance and intervention for HBOC patients, not only in Japan but also worldwide.

Restoration of ARID1A Protein in ARID1A-deficient Clear Cell Carcinoma of the Ovary Attenuates Reactivity to Cytotoxic T Lymphocytes.

Risa Tsunematsu, Aiko Murai, Yuka Mizue, Terufumi Kubo, Tasuku Mariya, Rena Morita, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Tsuyoshi Saito, Toshihiko Torigoe

Cancer genomics & proteomics 21 ( 4 ) 414 - 420 2024年 [国際誌]

BACKGROUND/AIM: Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor prognosis. ARID1A gene mutations, commonly found in ovarian clear cell carcinoma (OCCC), contribute to its pathogenesis. Recent data revealed that the ARID1A mutation is related to better outcomes of cancer immunotherapy. Thus, this study aimed to investigate the immunotherapy treatment susceptibility of OCCC bearing ARID1A mutations. MATERIALS AND METHODS: Expression of ARID1A was analyzed using western blotting in ovarian cancer cell lines. OCCC cell lines JHOC-9 and RMG-V were engineered to overexpress NY-ESO-1, HLA-A*02:01, and ARID1A. Sensitivity to chemotherapy and T cell receptor-transduced T (TCR-T) cells specific for NY-ESO-1 was assessed in ARID1A-restored cells compared to ARID1A-deficient wild-type cells. RESULTS: JHOC-9 cells and RMG-V cells showed no expression of ARID1A protein. Overexpression of ARID1A in JHOC-9 and RMG-V cells did not impact sensitivity to gemcitabine. While ARID1A overexpression decreased sensitivity to cisplatin in RMG-V cells, it had no such effect in JHOC-9 cells. ARID1A overexpression reduced the reactivity of NY-ESO-1-specific TCR-T cells, as observed by the IFNγ ESLIPOT assay. CONCLUSION: Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.

Pregnancy-specific beta-1-glycoprotein 6 is a potential novel diagnostic biomarker of placenta accreta spectrum.

Hazuki Kashiwagi, Tasuku Mariya, Mina Umemoto, Shiori Ogawa, Yoshihiko Hirohashi, Yuya Fujibe, Terufumi Kubo, Masayuki Someya, Tsuyoshi Baba, Shinichi Ishioka, Toshihiko Torigoe, Tsuyoshi Saito

Medical molecular morphology 2023年10月 [国内誌]

Early diagnosis is essential for the safer perinatal management of placenta accreta spectrum (PAS). We used transcriptome analysis to investigate diagnostic maternal serum biomarkers and the mechanisms of PAS development. We analyzed eight formalin-fixed paraffin-embedded placental specimens from two placenta increta and three placenta percreta cases who underwent cesarean hysterectomy at Sapporo Medical University Hospital between 2013 and 2019. Invaded placental regions were isolated from the uterine myometrium and RNA was extracted. The transcriptome difference between normal placenta and PAS was analyzed by microarray analysis. The PAS group showed markedly decreased expression of placenta-specific genes such as LGALS13 and the pregnancy-specific beta-1-glycoprotein (PSG) family. Term enrichment analysis revealed changes in genes related to cellular protein catabolic process, female pregnancy, autophagy, and metabolism of lipids. From the highly dysregulated genes in the PAS group, we investigated the expression of PSG family members, which are secreted into the intervillous space and can be detected in maternal serum from the early stage of pregnancy. The gene expression level of PSG6 in particular was progressively decreased from placenta increta to percreta. The PSG family, especially PSG6, is a potential biomarker for PAS diagnosis.

Endocrinological and Metabolic Heterogeneity is low in Japanese Women with Polycystic Ovary Syndrome.

Tsuyoshi Baba, Toshiaki Endo, Tasuku Mariya, Yoshika Kuno, Hiroyuki Honnma, Mika Kanaya, Tsuyoshi Saito

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 102217 - 102217 2023年09月 [国際誌]

OBJECTIVE: This study aims to evaluate the endocrine differences among polycystic ovary syndrome (PCOS) phenotypes in Japanese women. METHODS: 118 Japanese women that we diagnosed with PCOS agreed to be included in the study. The study group was classified into the following four phenotypes: A) hyperandrogenism (HA); ovulatory disorder (OvD) and polycystic ovary morphology (PCOM); B) HA and OvD; C) HA and PCOM; and D) OvD and PCOM. We also recruited 66 healthy Japanese women to the study as control participants. Age, body mass index, androgens, luteinizing hormone, follicle-stimulating hormone, and insulin resistance index were evaluated and compared. RESULTS: The proportions of phenotypes A, B, C, and D were 57/120 (47.5%), 4/120 (3.3%), 13/120 (10.8%), and 46/120 (38.3%), respectively. The proportion of phenotype B was too small; therefore, phenotypes A and B were grouped as classical PCOS for intergroup comparisons. The luteinizing hormone/follicle-stimulating hormone ratio in the classical PCOS group was higher than that in the phenotype D group (P < 0.001). Androgen concentrations in the phenotype D group were significantly lower than those in the other groups (P < 0.01). Phenotype D was more common in lean women with PCOS. The surrogate marker of insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) was not different irrespective of PCOS and its phenotypes. CONCLUSION: Except for androgens, endocrine differences by PCOS phenotype are not evident, suggesting that diversity among patients with PCOS is relatively low in Japanese women.

Breakpoints in complex chromosomal rearrangements correspond to transposase-accessible regions of DNA from mature sperm.

Takeshi Sugimoto, Hidehito Inagaki, Tasuku Mariya, Rie Kawamura, Mariko Taniguchi-Ikeda, Seiji Mizuno, Yukako Muramatsu, Ikuya Tsuge, Hirofumi Ohashi, Nakamichi Saito, Yuiko Hasegawa, Nobuhiko Ochi, Masatoshi Yamaguchi, Jun Murotsuki, Hiroki Kurahashi

Human genetics 2023年08月 [国際誌]

Constitutional complex chromosomal rearrangements (CCRs) are rare cytogenetic aberrations arising in the germline via an unknown mechanism. Here we analyzed the breakpoint junctions of microscopically three-way or more complex translocations using comprehensive genomic and epigenomic analyses. All of these translocation junctions showed submicroscopic genomic complexity reminiscent of chromothripsis. The breakpoints were clustered within small genomic domains with junctions showing microhomology or microinsertions. Notably, all of the de novo cases were of paternal origin. The breakpoint distributions corresponded specifically to the ATAC-seq (assay for transposase-accessible chromatin with sequencing) read data peak of mature sperm and not to other chromatin markers or tissues. We propose that DNA breaks in CCRs may develop in an accessible region of densely packaged chromatin during post-meiotic spermiogenesis.

Changes in preterm and extremely preterm birth rates in Japan after the introduction of obstetrical practice guidelines in 2008.

Satoshi Shimano, Takashi Yamada, Kazutoshi Cho, Kazuo Sengoku, Tasuku Mariya, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 2023年07月 [国際誌]

AIM: Obstetrical guidelines were established in Japan in 2008, and obstetrical diagnoses and treatments were subsequently standardized nationally. We examined changes in the preterm birth rate (PTBR) and extremely preterm birth rate (EPTBR) following the introduction of such guidelines. METHODS: Information on 50 706 432 live births in Japan between 1979 and 2021, including Japanese reproductive medicine, the childbearing age of pregnant women, and the employment status of reproductive-age women between 2007 and 2020, were obtained from the Japanese government and academic societies. Regression analysis was used to compare chronological changes nationally and those of eight Japanese regions. Regional and national average PTBRs and EPTBRs from 2007 to 2020 were compared by using a repeated measures analysis of variance. RESULTS: From 1979 to 2007, PTBRs and EPTBRs in Japan increased significantly. However, from 2008, the national PTBR and EPTBR decreased until 2020 (p < 0.001) and 2019 (p = 0.02), respectively. From 2007 to 2020, overall PTBR and EPTBR were 5.68% and 0.255%, respectively. A significant difference in the PTBR and EPTBR existed between the eight Japanese regions. During this period, the number of pregnancies using assisted reproductive technology increased from 19 595 to 60 381, pregnant women became older, the employment rate of those of reproductive age increased, and nonregular employment was 54%, which was 2.5 times higher than for men. CONCLUSIONS: In Japan, after obstetrical guidelines were enacted in 2008, PTRBs decreased significantly even under the pressure of increasing preterm births. Countermeasures may be necessary for regions showing high PTBRs.

深層学習によるHE染色データを用いた子宮内膜癌プロファイル判定の適否に関する検討

梅本美菜, 真里谷奨, 永田舞, 堀米俊弘, 新開翔太, 杉田真太朗, 金関貴幸, 松浦基樹, 岩崎雅宏, 廣橋良彦, 長谷川匡, 鳥越俊彦, 齋藤豪, 藤野雄一

日本医療情報学会春季学術大会プログラム・抄録集 ( (一社)日本医療情報学会 ) 27回 122 - 123 2023年06月

Clinical application of long-read nanopore sequencing in a preimplantation genetic testing pre-clinical workup to identify the junction for complex Xq chromosome rearrangement-related disease.

Tasuku Mariya, Yui Shichiri, Takeshi Sugimoto, Rie Kawamura, Syunsuke Miyai, Hidehito Inagaki, Eiji Sugihara, Keiko Ikeda, Tsuyoshi Baba, Aki Ishikawa, Michiko Ammae, Yoshiharu Nakaoka, Tsuyoshi Saito, Akihiro Sakurai, Hiroki Kurahashi

Prenatal diagnosis 43 ( 3 ) 304 - 313 2023年02月 [国際誌]

OBJECTIVE: Xq chromosome duplication with complex rearrangements is generally acknowledged to be associated with neurodevelopmental disorders such as Pelizaeus-Merzbacher disease (PMD) and MECP2 duplication syndrome. For couples who required a PGT-M (pre-implantation genetic testing for monogenic disease) for these disorders, junction-specific PCR is useful to directly detect pathogenic variants. Therefore, pre-clinical workup for PGT-M requires the identification of the junction of duplicated segments in PMD and MECP2 duplication syndrome, which is generally difficult. METHODS: In this report, we used nanopore long-read sequencing targeting the X chromosome using an adaptive sampling method to identify breakpoint junctions in disease-causing triplications. RESULTS: By long-read sequencing, we successfully identified breakpoint junctions in one PMD case with PLP1 triplication and in another MECP2 triplication case in a single sequencing run. Surprisingly, the duplicated region involving MECP2 was inserted 45 Mb proximal to the original position. This inserted region was confirmed by FISH analysis. With the help of precise mapping of the pathogenic variant, we successfully re-established STR haplotyping for PGT-M and avoided any potential misinterpretation of the pathogenic allele due to recombination. CONCLUSION: Long-read sequencing with adaptive sampling in a PGT-M pre-clinical workup is a beneficial method for identifying junctions of chromosomal complex structural rearrangements. This article is protected by copyright. All rights reserved.

深層学習を用いたHE染色からの子宮内膜癌分子生物学的プロファイル推定の適否に関する検討

梅本美菜, 真里谷奨, 新開翔太, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 260 2023年02月

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