The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Luciano G Martelotto - One of the best experts on this subject based on the ideXlab platform.

  • recurrent hotspot mutations in hras q61 and pi3k akt pathway genes as drivers of breast Adenomyoepitheliomas
    Nature Communications, 2018
    Co-Authors: Felipe C Geyer, Pier Selenica, Marcia Edelweiss, Anastasios D Papanastasiou, Alison Smith, Kathleen A Burke, H Y Wen, Salvatore Piscuoglio, Anne M Schultheis, Luciano G Martelotto
    Abstract:

    Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, of which a subset will progress to invasive or metastatic cancer. We sought to define the genomic landscape of Adenomyoepitheliomas. Massively parallel sequencing revealed highly recurrent somatic mutations in HRAS and PI3K-AKT pathway-related genes. Strikingly, HRAS mutations were restricted to estrogen receptor (ER)-negative tumors, all affected codon 61, and all but one co-occurred with PIK3CA or PIK3R1 mutations. To interrogate the functional significance of HRAS Q61 mutations in adenomyoepithelial differentiation, we expressed HRASQ61R alone or in combination with PIK3CAH1047R in non-transformed ER-negative breast epithelial cells. HRASQ61R induced characteristic phenotypes of Adenomyoepitheliomas such as the expression of myoepithelial markers and loss of e-cadherin, hyperactivation of AKT signaling, and transformative properties that were arrested by combination therapy with AKT and MEK inhibitors. Our results indicate that breast Adenomyoepitheliomas often manifest a unique transformation program featuring HRAS activation.

Debra S Heller - One of the best experts on this subject based on the ideXlab platform.

  • malignant Adenomyoepithelioma of the breast with malignant proliferation of epithelial and myoepithelial elements a case report and review of the literature
    Archives of Pathology & Laboratory Medicine, 2000
    Co-Authors: Atif A Ahmed, Debra S Heller
    Abstract:

    Malignant Adenomyoepithelioma of the breast is a rare lesion characterized by malignant proliferation of epithelial and myoepithelial cells that show characteristic histologic and immunohistochemical features. Eleven cases have been reported, 4 of which showed evidence of distant metastasis. The authors report a case of malignant Adenomyoepithelioma in the axillary tail of a 71-year-old woman, one of the oldest patients described so far, and review the literature. Malignancy in the current case was evidenced by the presence of local invasion, high mitotic rate, and severe cytologic atypia. The tumor was associated with adenosis and lobular adenomyoepithelial hyperplasia. Malignant Adenomyoepithelioma is a rare neoplasm, diagnosable by light microscopy and immunohistochemistry. To date, it has only been reported in women, who ranged in age from 26 to 76 years. Metastases have only been documented in tumors 2.0 cm in diameter or larger.

Felipe C Geyer - One of the best experts on this subject based on the ideXlab platform.

  • assessment of hmga2 and plag1 rearrangements in breast Adenomyoepitheliomas
    NPJ breast cancer, 2019
    Co-Authors: Fresia Pareja, Felipe C Geyer, Pier Selenica, Marcia Edelweiss, David N. Brown, Arnaud Da Cruz Paula, Hannah Y. Wen, Ana Paula Martins Sebastiao, Rodrigo Gulartemerida, Achim A Jungbluth
    Abstract:

    Breast Adenomyoepitheliomas (AMEs) are rare epithelial-myoepithelial neoplasms that may occasionally produce myxochondroid matrix, akin to pleomorphic adenomas (PAs). Regardless of their anatomic location, PAs often harbor rearrangements involving HMGA2 or PLAG1. We have recently shown that the repertoire of somatic genetic alterations of AMEs varies according to their estrogen receptor (ER) status; whilst the majority of ER-positive AMEs display mutually exclusive PIK3CA or AKT1 hotspot mutations, up to 60% of ER-negative AMEs harbor concurrent HRAS Q61 hotspot mutations and mutations affecting either PIK3CA or PIK3R1. Here, we hypothesized that a subset of AMEs lacking these somatic genetic alterations could be underpinned by oncogenic fusion genes, in particular those involving HMGA2 or PLAG1. Therefore, we subjected 13 AMEs to RNA-sequencing for fusion discovery (n = 5) and/or fluorescence in situ hybridization (FISH) analysis for HMGA2 and PLAG1 rearrangements (n = 13). RNA-sequencing revealed an HMGA2-WIF1 fusion gene in an ER-positive AME lacking HRAS, PIK3CA and AKT1 somatic mutations. This fusion gene, which has been previously described in salivary gland PAs, results in a chimeric transcript composed of exons 1–5 of HMGA2 and exons 3–10 of WIF1. No additional in-frame fusion genes or HMGA2 or PLAG1 rearrangements were identified in the remaining AMEs analyzed. Our results demonstrate that a subset of AMEs lacking mutations affecting HRAS and PI3K pathway-related genes may harbor HMGA2-WIF1 fusion genes, suggesting that a subset of breast AMEs may be genetically related to PAs or that a subset of AMEs may originate in the context of a PA. A subset of benign breast tumors known as Adenomyoepitheliomas may be driven by gene fusions found in related cancers elsewhere in the body. Adenomyoepitheliomas are rare benign tumors characterized by the proliferation of both luminal epithelial cells and adjacent myoepithelial cells. Since these tumors resemble a common type of salivary gland cancer called pleomorphic adenoma that often harbors genomic rearrangements involving two particular genes, Jorge Reis-Filho from Memorial Sloan Kettering Cancer Center in New York City, USA, and colleagues looked for similar oncogenic fusions in 13 breast Adenomyoepitheliomas with no known causative genetic alterations. They identified a gene fusion in one of their 13 tumor samples, suggesting that a subset of Adenomyoepitheliomas may be genetically related to pleomorphic adenomas. The findings could aid in future treatment of both diseases.

  • Assessment of HMGA2 and PLAG1 rearrangements in breast Adenomyoepitheliomas
    Nature Publishing Group, 2019
    Co-Authors: Fresia Pareja, Felipe C Geyer, Pier Selenica, Marcia Edelweiss, David N. Brown, Ana Martins P. Sebastião, Rodrigo Gularte-mérida, Arnaud Da Cruz Paula, Hannah Y. Wen
    Abstract:

    Genetics: uncommon breast tumors linked genetically to salivary gland cancer A subset of benign breast tumors known as Adenomyoepitheliomas may be driven by gene fusions found in related cancers elsewhere in the body. Adenomyoepitheliomas are rare benign tumors characterized by the proliferation of both luminal epithelial cells and adjacent myoepithelial cells. Since these tumors resemble a common type of salivary gland cancer called pleomorphic adenoma that often harbors genomic rearrangements involving two particular genes, Jorge Reis-Filho from Memorial Sloan Kettering Cancer Center in New York City, USA, and colleagues looked for similar oncogenic fusions in 13 breast Adenomyoepitheliomas with no known causative genetic alterations. They identified a gene fusion in one of their 13 tumor samples, suggesting that a subset of Adenomyoepitheliomas may be genetically related to pleomorphic adenomas. The findings could aid in future treatment of both diseases

  • recurrent hotspot mutations in hras q61 and pi3k akt pathway genes as drivers of breast Adenomyoepitheliomas
    Nature Communications, 2018
    Co-Authors: Felipe C Geyer, Pier Selenica, Marcia Edelweiss, Anastasios D Papanastasiou, Alison Smith, Kathleen A Burke, H Y Wen, Salvatore Piscuoglio, Anne M Schultheis, Luciano G Martelotto
    Abstract:

    Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, of which a subset will progress to invasive or metastatic cancer. We sought to define the genomic landscape of Adenomyoepitheliomas. Massively parallel sequencing revealed highly recurrent somatic mutations in HRAS and PI3K-AKT pathway-related genes. Strikingly, HRAS mutations were restricted to estrogen receptor (ER)-negative tumors, all affected codon 61, and all but one co-occurred with PIK3CA or PIK3R1 mutations. To interrogate the functional significance of HRAS Q61 mutations in adenomyoepithelial differentiation, we expressed HRASQ61R alone or in combination with PIK3CAH1047R in non-transformed ER-negative breast epithelial cells. HRASQ61R induced characteristic phenotypes of Adenomyoepitheliomas such as the expression of myoepithelial markers and loss of e-cadherin, hyperactivation of AKT signaling, and transformative properties that were arrested by combination therapy with AKT and MEK inhibitors. Our results indicate that breast Adenomyoepitheliomas often manifest a unique transformation program featuring HRAS activation.

  • Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast Adenomyoepitheliomas
    Nature Publishing Group, 2018
    Co-Authors: Felipe C Geyer, Pier Selenica, Marcia Edelweiss, Anastasios D Papanastasiou, Alison Smith, Kathleen A Burke, Salvatore Piscuoglio, Huei-chi Wen, Anne M Schultheis
    Abstract:

    Adenomyoepithelioma is a rare tumor of the breast with an unknown genetic basis. Here the authors perform a genomic analysis of Adenomyoepitheliomas revealing that their repertoire of somatic mutations vary according to the estrogen receptor (ER) status, and that ER-negative tumors harbor recurrent mutations in HRAS and PI3K pathway genes

P Moerman - One of the best experts on this subject based on the ideXlab platform.

  • adenoid cystic carcinoma arising in an Adenomyoepithelioma of the breast
    Virchows Archiv, 1998
    Co-Authors: J Van Dorpe, Annemie De Pauw, P Moerman
    Abstract:

    Adenomyoepithelioma is a mixed epithelial and myoepithelial tumour. In rare cases Adenomyoepitheliomas give rise to carcinomas with epithelial, myoepithelial, or mixed epithelial and myoepithelial differentiation. Carcinomas arising in Adenomyoepithelioma range from low grade to high grade, and 15 cases have been reported in the literature. We describe a 36-year-old woman with a very rare adenoid cystic carcinoma arising in a tubular Adenomyoepithelioma. The histogenesis of carcinoma arising in an Adenomyoepithelioma is discussed.

Anupma Nayak - One of the best experts on this subject based on the ideXlab platform.

  • clinical characteristics and outcomes of benign atypical and malignant breast Adenomyoepithelioma a single institution s experience
    American Journal of Surgery, 2020
    Co-Authors: Naomi Wiens, Daniel I Hoffman, Cassie Y Huang, Anupma Nayak, Julia Tchou
    Abstract:

    Abstract Background Breast Adenomyoepithelioma (AME) is rare. We sought to evaluate clinical characteristics, treatment, and outcomes of a contemporary patient cohort stratified by histology. Methods We queried health records containing “Adenomyoepithelioma” between 2000 and 2018. Histology was confirmed with centralized review and classified into benign, atypical, and malignant. Clinical characteristics, demographics, treatment, and oncologic outcomes were compared. Results Our query yielded 24 patients with adenomyoethelioma. Histologic diagnosis was confirmed in 12 (benign n = 6, atypical n = 3, malignant n = 3). Excision (n = 11) was the usual initial treatment, with margin status available in 10 patients. Mean follow up was 44 months (range 1–138 months) with no local recurrence observed. Two patients with benign AME presented with concurrent contralateral breast cancer, and one with malignant AME died of metastatic AME. Conclusion Wide excision of atypical and malignant AME is recommended as local recurrence when excised completely was not observed. Given metastatic potential of malignant AME, multimodal therapy may be warranted.

  • Adenomyoepitheliomas of the breast frequently harbor recurrent hotspot mutations in pik3 akt pathway related genes and a subset show genetic similarity to salivary gland epithelial myoepithelial carcinoma
    The American Journal of Surgical Pathology, 2019
    Co-Authors: Daniel Lubin, Erik Toorens, Paul J Zhang, Shabnam Jaffer, Ezra Baraban, Ira J Bleiweiss, Anupma Nayak
    Abstract:

    Adenomyoepitheliomas (AME) of the breast and epithelial-myoepithelial carcinomas (EMCs) of salivary gland are morphologically similar tumors defined by the presence of a biphasic population of ductal epithelial elements mixed with myoepithelial cells. We sought to explore the molecular profile of AM