Journal of Pathology and Translational Medicine

Original Article

Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists: Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee; J Pathol Transl Med. 2023;57(5):265-272. Published online September 15, 2023; DOI: https://doi.org/10.4132/jptm.2023.08.26

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Abstract PDF: Background
The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education.
Methods
The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education.
Results
The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated.
Conclusions
Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.

Review

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms: Dong-Wook Kang, Baek-hui Kim, Joon Mee Kim, Jihun Kim, Hee Jin Chang, Mee Soo Chang, Jin-Hee Sohn, Mee-Yon Cho, So-Young Jin, Hee Kyung Chang, Hye Seung Han, Jung Yeon Kim, Hee Sung Kim, Do Youn Park, Ha Young Park, So Jeong Lee, Wonae Lee, Hye Seung Lee, Yoo Na Kang, Younghee Choi; J Pathol Transl Med. 2021;55(4):247-264. Published online July 8, 2021; DOI: https://doi.org/10.4132/jptm.2021.05.28

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Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Citations

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Lower Gastrointestinal Bleeding Secondary to Appendiceal Mucinous Neoplasm: A Report of Two Cases and a Review of the Literature
Jesús Omar Soto Llanes, Samanta Kin Dosal Limón, Ana Jimena Iberri Jaime, Mario Zambrano Lara, Billy Jiménez Bobadilla
Cureus.2024;[Epub] CrossRef
Appendiceal perforation secondary to endometriosis with intestinal metaplasia: A case report
Minghua Wang, Jing Liu, Boxin Hu, Simin Wang, Ping Xie, Ping Li
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Primary and secondary tumors of the peritoneum: key imaging features and differential diagnosis with surgical and pathological correlation
Javier Miguez González, Francesc Calaf Forn, Laura Pelegrí Martínez, Pilar Lozano Arranz, Rafael Oliveira Caiafa, Jordi Català Forteza, Lina Maria Palacio Arteaga, Ferrán Losa Gaspà, Isabel Ramos Bernadó, Pedro Barrios Sánchez, Juan Ramón Ayuso Colella
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Muzinöse Tumoren des Peritoneums
Anne Kristin Fischer, Andrea Tannapfel, Alexander Quaas
Die Chirurgie.2023; 94(10): 823. CrossRef
Landscape of Genetic Mutations in Appendiceal Cancers
Marian Constantin, Cristina Mătanie, Livia Petrescu, Alexandra Bolocan, Octavian Andronic, Coralia Bleotu, Mihaela Magdalena Mitache, Sorin Tudorache, Corneliu Ovidiu Vrancianu
Cancers.2023; 15(14): 3591. CrossRef
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Original Articles

Differential MicroRNA Expression between EGFR T790M and L858R Mutated Lung Cancer: Ji Yeon Kim, Woo Jeong Lee, Ha Young Park, Ahrong Kim, Dong Hoon Shin, Chang Hun Lee; J Pathol Transl Med. 2018;52(5):275-282. Published online August 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.29

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Abstract PDF Supplementary Material

Background
MicroRNAs (miRNAs) are short, non-coding RNAs that mediate post-transcriptional gene regulation. They are commonly deregulated in human malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to investigate miRNA expression in T790M-mutated NSCLC resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.
Methods
Six cases of resected NSCLC harboring the T790M mutation were examined. We performed miRNA time polymerase chain reaction (PCR) array profiling using EGFR T790M-mutated NSCLC and L858R-mutated NSCLC. Once identified, miRNAs that were differentially expressed between the two groups were validated by quantitative real-time polymerase chain reaction (qRT-PCR).
Results
miRNA PCR array profiling revealed three up-regulated miRNAs whose expression levels were altered 4.0-fold or more in the EGFR T790M mutation group than in the L858R group: miR-1 (fold change, 4.384), miR-196a (fold change, 4.138), and miR-124 (fold change, 4.132). The three differentially expressed miRNAs were validated by qRT-PCR, and they were found to be overexpressed in the T790M group relative to L858R group. In particular, expression levels of miR-1 and miR-124 were significantly higher in the T790M group (p-value of miR-1 = .004, miR-124 = .007, miR-196a = .096).
Conclusions
MiR-1, miR-124, and miR-196a are overexpressed in EGFR T790M mutated NSCLC.

Citations

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Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages
Hao Ho, Sung-Liang Yu, Hsuan-Yu Chen, Shin-Sheng Yuan, Kang-Yi Su, Yi-Chiung Hsu, Chung-Ping Hsu, Cheng-Yen Chuang, Ya-Hsuan Chang, Yu-Cheng Li, Chiou-Ling Cheng, Gee-Chen Chang, Pan-Chyr Yang, Ker-Chau Li
Lung Cancer.2023; 184: 107352. CrossRef
Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
Alessandro Leonetti, Mjriam Capula, Roberta Minari, Giulia Mazzaschi, Alessandro Gregori, Btissame El Hassouni, Filippo Papini, Paola Bordi, Michela Verzè, Amir Avan, Marcello Tiseo, Elisa Giovannetti
Cells.2021; 10(6): 1520. CrossRef
Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line
Nalini Devi Verusingam, Yi-Chen Chen, Heng-Fu Lin, Chao-Yu Liu, Ming-Cheng Lee, Kai-Hsi Lu, Soon-Keng Cheong, Alan Han-Kiat Ong, Shih-Hwa Chiou, Mong-Lien Wang
Journal of the Chinese Medical Association.2021; 84(3): 248. CrossRef
Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands
Sarah Sayed Hassanein, Sherif Abdelaziz Ibrahim, Ahmed Lotfy Abdel-Mawgood
International Journal of Molecular Sciences.2021; 22(22): 12496. CrossRef
The Roles of MicroRNA in Lung Cancer
Kuan-Li Wu, Ying-Ming Tsai, Chi-Tun Lien, Po-Lin Kuo, Jen-Yu Hung
International Journal of Molecular Sciences.2019; 20(7): 1611. CrossRef

Chronic Placental Inflammation in Twin Pregnancies: Heejin Bang, Go Eun Bae, Ha Young Park, Yeon Mee Kim, Suk-Joo Choi, Soo-young Oh, Cheong-Rae Roh, Jung-Sun Kim; J Pathol Transl Med. 2015;49(6):489-496. Published online October 13, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.09

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Abstract PDF

Background
Chronic placental inflammation, such as villitis of unknown etiology (VUE) and chronic chorioamnionitis (CCA), is considered a placental manifestation of maternal anti-fetal rejection. The aim of this study is to investigate its frequency in twin pregnancies compared to singleton pregnancies. Methods: Three hundred twin placentas and 1,270 singleton placentas were consecutively collected at a tertiary medical center in Seoul, Republic of Korea from 2009 to 2012. Hematoxylin and eosin sections of tissue samples (full-thickness placental disc and chorioamniotic membranes) were reviewed. Results: Non-basal VUE was more frequent in twin placentas than in singleton placentas (6.0% vs 3.2%, p < .05). In preterm birth, CCA was found less frequently in twin placentas than in singleton placentas (9.6% vs 14.8%, p < .05), reaching its peak at an earlier gestational age in twin placentas (29–32 weeks) than in singleton placentas (33–36 weeks). CCA was more frequent in twin pregnancies with babies of a different sex than with those with the same sex (13.8% vs 6.9%, p = .052). Separate dichorionic diamniotic twin placentas were affected by chronic deciduitis more frequently than singleton placentas (16.9% vs 9.7%, p < .05). Conclusions: The higher frequency of non-basal VUE in twin placentas and of CCA in twin placentas with different fetal sex supports the hypothesis that the underlying pathophysiological mechanism is maternal anti-fetal rejection related to increased fetal antigens in twin pregnancies. The peak of CCA at an earlier gestational age in twin placentas than in singleton placentas suggests that CCA is influenced by placental maturation.

Citations

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Villitis of unknown etiology, chronic deciduitis, chronic chorioamnionitis and chronic histiocytic intervillositis in monozygotic and dizygotic twin pregnancies. A retrospective analysis of 16 cases
Henning Feist, Ulrich Lehmann, Simin Bajwa, Corinna Brüschke, Nora Schaumann
Placenta.2023; 133: 32. CrossRef
Discordant Eosinophilic/T-Cell Chorionic Vasculitis in a Dichorionic Diamniotic Placenta
Evelina Silvestri, Francesca Servadei, Ione Tamagnini, Laura Moretti, Maria Paola Bonasoni
International Journal of Molecular Sciences.2023; 24(11): 9207. CrossRef
Histopathologic evaluation of dichorionic twin placentas in unassisted and in vitro fertilized pregnancies affected by preeclampsia
Evelina Manvelyan, Karmaine A. Millington, Baruch S. Abittan, Matthew J. Blitz, Brittany Kwait, Weiwei Shan, Randi H. Goldman
The Journal of Maternal-Fetal & Neonatal Medicine.2022; 35(26): 10262. CrossRef
Microbiological safety of the Dr. Arabin cervical pessary in pregnant women with short cervix
Gabriel S. Sargsyan, Olesya N. Bespalova, Alevtina M. Savicheva, Tatyana A. Khusnutdinova, Olga V. Budilovskaya, Anna A. Krysanova, Kira V. Shalepo
Journal of obstetrics and women's diseases.2022; 71(5): 65. CrossRef
Disorders of placental villous maturation in fetal death
Sunil Jaiman, Roberto Romero, Percy Pacora, Eunjung Jung, Gaurav Bhatti, Lami Yeo, Yeon Mee Kim, Bomi Kim, Chong Jai Kim, Jung-Sun Kim, Faisal Qureshi, Suzanne M. Jacques, Offer Erez, Nardhy Gomez-Lopez, Chaur-Dong Hsu
Journal of Perinatal Medicine.2020;[Epub] CrossRef
Biochemical predictors of preterm birth in twin pregnancies: A systematic review involving 6077 twin pregnancies
Shemoon Marleen, Chamalika Dias, Rebecca MacGregor, John Allotey, Joseph Aquilina, Asma Khalil, Shakila Thangaratinam
European Journal of Obstetrics & Gynecology and Reproductive Biology.2020; 250: 130. CrossRef
Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
Duško Kljakić, Miloš Z. Milosavljević, Milan Jovanović, Vesna Čolaković Popović, Saša Raičević
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The frequency and clinical significance of intra-amniotic inflammation in twin pregnancies with preterm labor and intact membranes
Kyung Joon Oh, Joon-Seok Hong, Roberto Romero, Bo Hyun Yoon
The Journal of Maternal-Fetal & Neonatal Medicine.2019; 32(4): 527. CrossRef
Discordance of Twin Placentas for Multifocal Eosinophilic/T-cell Chorionic Vasculitis
Erik W Nohr, James R Wright
Pediatric and Developmental Pathology.2019; 22(1): 40. CrossRef
Differential immunophenotype of macrophages in acute and chronic chorioamnionitis
Go-Eun Bae, Joon-Seok Hong, Jung-Sun Kim, Ha Young Park, Ja Yun Jang, Yi Seul Kim, Suk-Joo Choi, Soo-young Oh, Cheong-Rae Roh
Journal of Perinatal Medicine.2017; 45(4): 483. CrossRef
Fetal death: an extreme manifestation of maternal anti-fetal rejection
Kia Lannaman, Roberto Romero, Tinnakorn Chaiworapongsa, Yeon Mee Kim, Steven J. Korzeniewski, Eli Maymon, Nardhy Gomez-Lopez, Bogdan Panaitescu, Sonia S. Hassan, Lami Yeo, Bo Hyun Yoon, Chong Jai Kim, Offer Erez
Journal of Perinatal Medicine.2017; 45(7): 851. CrossRef

Case Studies

Congenital Peribronchial Myofibroblastic Tumor: A Case Study and Literature Review: Yuil Kim, Ha Young Park, Junhun Cho, Joungho Han, Eun Yoon Cho; Korean J Pathol. 2013;47(2):172-176. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.172

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Abstract PDF

Congenital peribronchial myofibroblastic tumor (CPMT) is a benign pulmonary spindle cell neoplasm of intrauterine and perinatal period, which is thought to arise from primitive peribronchial mesenchyme. We present a case detected incidentally in a one-month-old infant. The solid and partially necrotic tumor involved the right middle and lower lobes of the lung with extension to the diaphragm. Histologically, the tumor was composed of fasciculated monotonous spindle cells, proliferating peribronchiolar cartilage and round cells with rich vasculature, and high mitotic activity was identified in the round cell area. Immunohistochemical and electron microscopic studies showed that the spindle cells were myofibroblastic in phenotype. Although the tumor showed several malignant pathological features, recurrence was not observed in the two-year follow-up period, consistent with the benign clinical behavior of CPMT.

Citations

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Congenital peribronchial myofibroblastic tumor (CPMT): a case report with long term follow-up and next-generation sequencing (NGS)
Ping Zhou, Shuang Li, Weiya Wang, Yuan Tang, Lili Jiang
BMC Pediatrics.2023;[Epub] CrossRef
Neonatal congenital lung tumors — the importance of mid-second-trimester ultrasound as a diagnostic clue
Stephan L. Waelti, Laurent Garel, Dorothée Dal Soglio, Françoise Rypens, Michael Messerli, Josée Dubois
Pediatric Radiology.2017; 47(13): 1766. CrossRef
Congenital peribronchial myofibroblastic tumor: Case report and review of literature
Jolanta Jedrzkiewicz, Eric Scaife, Bo Hong, Sarah South, Mouied Alashari
Journal of Pediatric Surgery Case Reports.2015; 3(4): 154. CrossRef
Perinatal Thoracic Mass Lesions: Pre- and Postnatal Imaging
Evan J. Zucker, Monica Epelman, Beverley Newman
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Prenatal imaging and immunohistochemical analysis of congenital peribronchial myofibroblastic tumor
Y.‐A. Tu, W.‐C. Lin, H.‐J. Chen, J.‐C. Shih
Ultrasound in Obstetrics & Gynecology.2015; 46(2): 247. CrossRef
A Congenital Peribronchial Myofibroblastic Tumor Detected in a Premature Infant at 28 Weeks but That Resolved in the Late Stage of Pregnancy
Bo Xia, Gang Yu, Chun Hong, Lei Zhang, Jing Tang, Cuifen Liu
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Congenital peribronchial myofibroblastic tumor
Yuka Hotokebuchi, Kenichi Kohashi, Satoshi Toyoshima, Naoko Matsumoto, Toshinori Nakashima, Yoshinao Oda
Pathology International.2014; 64(4): 189. CrossRef

Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination: Go Eun Bae, Nara Yoon, Ha Young Park, Sang Yun Ha, Junhun Cho, Yunkyung Lee, Kyoung-Mee Kim, Cheol Keun Park; Korean J Pathol. 2013;47(2):163-166. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.163

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Abstract PDF

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 µm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.

Citations

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Caecal malakoplakia: a rare mimic of malignancy
Jeffrey Li Voon Chong, Noor Ali
BMJ Case Reports.2024; 17(1): e257130. CrossRef
A Surgical Challenge Generated by Colonic Malakoplakia in Disguise as a Locally Advanced Colonic Malignancy—A Case Report
Cristina Șerban, Alexandra Toma, Dragoș Cristian Voicu, Constantin Popazu, Dorel Firescu, George Țocu, Raul Mihailov, Laura Rebegea
Medicina.2023; 59(1): 156. CrossRef
Colonic malakoplakia in a cardiac transplant recipient: A case report
Sadiya Shafijan
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Immunosuppressive drugs and the gastrointestinal tract in renal transplant patients
Merel M. Tielemans, Gerben A.J. van Boekel, Teun van Gelder, Eric T. Tjwa, Luuk B. Hilbrands
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Malakoplakia of the colon following renal transplantation in a 73 year old woman: report of a case presenting as intestinal perforation
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Colonic malakoplakia in a liver transplant recipient: A case report
Rana Ajabnoor, Mohammad Mawardi, Abdulmonem Almutawa
Human Pathology: Case Reports.2019; 18: 200323. CrossRef
Malakoplakia after kidney transplantation: Case report and literature review
John Fredy Nieto‐Ríos, Isabel Ramírez, Mónica Zuluaga‐Quintero, Lina María Serna‐Higuita, Federico Gaviria‐Gil, Alejandro Velez‐Hoyos
Transplant Infectious Disease.2017;[Epub] CrossRef
Megalocytic Interstitial Nephritis Following Acute Pyelonephritis with Escherichia coli Bacteremia: A Case Report
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Journal of Korean Medical Science.2015; 30(1): 110. CrossRef

Original Article

Methylation and Immunoexpression of p16^INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16^INK4a Hypermethylation in Plasma by Real-Time PCR: Jae Jun Lee, Eunkyung Ko, Junhun Cho, Ha Young Park, Jeong Eon Lee, Seok Jin Nam, Duk-Hwan Kim, Eun Yoon Cho; Korean J Pathol. 2012;46(6):554-561. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.554

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Abstract PDF

Background

The p16^INK4a gene methylation has been reported to be a major tumorigenic mechanism.

Methods

We evaluated the methylation status of the p16^INK4a genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16^INK4a DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay.

Results

The frequencies of p16^INK4a methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90), respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16^INK4a was significantly higher in the cancer patients than the normal controls (p<0.001).

Conclusions

High p16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16^INK4a promoter methylation in both invasive and intraductal carcinomas, suggesting it may be involved in the pathogenesis of breast cancer.

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Epigenetic modulation of BRCA‐1 and MGMT genes, and histones H4 and H3 are associated with breast tumors
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