Tinge Lei1, Mengjia Shen2, Xu Deng1, Yongqiang Shi1, Yan Peng1, Hui Wang1, Tongbing Chen3. 1. Department of Pathology, The Third Affiliated Hospital of Soochow University, 213003, Changzhou, Jiangsu, P.R. China. 2. Department of Pathology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, 610041, Chengdu, Sichuan, China. 3. Department of Pathology, The Third Affiliated Hospital of Soochow University, 213003, Changzhou, Jiangsu, P.R. China. 11030523@163.com.
Abstract
BACKGROUND: The genomic landscape of breast malignant phyllodes tumors (PTs) is not well defined, especially pregnancy-related malignant PTs. To clarify this topic, whole-exome next-generation sequencing (NGS) was performed on tumor samples and paired normal breast tissues from two pregnancy-related malignant PTs, followed by a functional analysis of the genetic alterations. METHODS: DNA from malignant PT samples and matched normal breast tissues of both patients were subjected to molecular profiling. NGS of the whole-exome was performed in a commercial molecular pathology laboratory. Predictive tools were used to estimate genetic variation in somatic and germline genes. RESULTS: In total, 29 somatic genomic alterations and 18 germline alterations were found in both patients. In Patient 1, 12 aberrations were identified in the tumor tissue, and 9 alterations were identified in matched normal breast tissue. One pathogenic variant in tumor suppressor genes (TP53) was detected in patient 1. In Patient 2, 18 and 10 variants were found in the tumor and matched normal breast tissue, respectively. In Patient 2, pathogenic alterations were identified in two tumor suppressor genes (PTEN and TP53). PTEN and TP53 may be potential drug targets. The functional predictive tools showed that genes of unknown significance for PTs, including FCHO1 in Patient 1, and LRP12 and PKM in Patient 2, were pathogenic. Several genes, including FCHO1, LRP12 and PKM, were shown for the first time to be altered in malignant PTs. A potentially pathogenic germline variant in PRF1, was detected in Patient 1. CONCLUSION: Our study first demonstrated somatic and germline gene alterations in two malignant PTs during pregnancy and lactation. These two PTs shared major genetic events, including TP53 mutation, which commonly occurs in malignant PTs; additionally, we identified two potential genes for targeted therapy, TP53 and PTEN. One germline mutation in PRF1 was also detected. These results provide clues regarding tumor pathogenesis and precision therapy development.
BACKGROUND: The genomic landscape of breast malignant phyllodes tumors (PTs) is not well defined, especially pregnancy-related malignant PTs. To clarify this topic, whole-exome next-generation sequencing (NGS) was performed on tumor samples and paired normal breast tissues from two pregnancy-related malignant PTs, followed by a functional analysis of the genetic alterations. METHODS: DNA from malignant PT samples and matched normal breast tissues of both patients were subjected to molecular profiling. NGS of the whole-exome was performed in a commercial molecular pathology laboratory. Predictive tools were used to estimate genetic variation in somatic and germline genes. RESULTS: In total, 29 somatic genomic alterations and 18 germline alterations were found in both patients. In Patient 1, 12 aberrations were identified in the tumor tissue, and 9 alterations were identified in matched normal breast tissue. One pathogenic variant in tumor suppressor genes (TP53) was detected in patient 1. In Patient 2, 18 and 10 variants were found in the tumor and matched normal breast tissue, respectively. In Patient 2, pathogenic alterations were identified in two tumor suppressor genes (PTEN and TP53). PTEN and TP53 may be potential drug targets. The functional predictive tools showed that genes of unknown significance for PTs, including FCHO1 in Patient 1, and LRP12 and PKM in Patient 2, were pathogenic. Several genes, including FCHO1, LRP12 and PKM, were shown for the first time to be altered in malignant PTs. A potentially pathogenic germline variant in PRF1, was detected in Patient 1. CONCLUSION: Our study first demonstrated somatic and germline gene alterations in two malignant PTs during pregnancy and lactation. These two PTs shared major genetic events, including TP53 mutation, which commonly occurs in malignant PTs; additionally, we identified two potential genes for targeted therapy, TP53 and PTEN. One germline mutation in PRF1 was also detected. These results provide clues regarding tumor pathogenesis and precision therapy development.
Authors: Jerzy Mituś; Marian Reinfuss; Jerzy W Mituś; Jerzy Jakubowicz; Pawel Blecharz; Wojciech M Wysocki; Piotr Skotnicki Journal: Breast J Date: 2014-09-17 Impact factor: 2.431
Authors: O Kenneth Macdonald; Christopher M Lee; Jonathan D Tward; Craig D Chappel; David K Gaffney Journal: Cancer Date: 2006-11-01 Impact factor: 6.860
Authors: Felipe C Geyer; Kathleen A Burke; Salvatore Piscuoglio; Charlotte K Y Ng; Anastasios D Papanastasiou; Caterina Marchiò; Pier Selenica; Marcia Edelweiss; Melissa P Murray; Edi Brogi; Robert A Soslow; Brian P Rubin; Larry Norton; Jorge S Reis-Filho; Britta Weigelt Journal: Mol Oncol Date: 2017-05-16 Impact factor: 6.603