MARIA LUCIA HIRATA KATAYAMA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
10 resultados
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- Somatic mutations in early onset luminal breast cancer(2018) ENCINAS, G.; SABELNYKOVA, V. Y.; LYRA, E. C. de; KATAYAMA, M. L. H.; MAISTRO, S.; VALLE, P. W. M. V.; PEREIRA, G. F. L.; RODRIGUES, L. M.; SERIO, P. A. M. P.; GOUVêA, A. C. R. C. de; GEYER, F. C.; BASSO, R. A.; PASINI, F. S.; DIZ, M. P. E.; BRENTANI, M. M.; GóES, J. C. G. S.; CHAMMAS, R.; BOUTROS, P. C.; FOLGUEIRA, M. A. A. K.Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal (HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA1/2 germline mutation carriers. Of the non-BRCA tumors, eight with luminal subtype (HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4. Potential cancer drivers affected in the present non-BRCA tumors include GRHL2, PIK3AP1, CACNA1E, SEMA6D, SMURF2, RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1, MUTYH, PALB2, POLD1, POLE, RAD9A, RAD51 and TP53, and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation. © Encinas et al.
- Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer(2019) KATAYAMA, Maria Lucia Hirata; VIEIRA, Rene Aloisio Costa; ANDRADE, Victor Piana; ROELA, Rosimeire Aparecida; LIMA, Luiz Guilherme Cernaglia Aureliano; KERR, Ligia Maria; CAMPOS, Adriano Polpo de; PEREIRA, Carlos Alberto de Braganca; SERIO, Pedro Adolpho de Menezes Pacheco; ENCINAS, Giselly; MAISTRO, Simone; PETRONI, Matheus de Almeida Leite; BRENTANI, Maria Mitzi; FOLGUEIRA, Maria Aparecida Azevedo KoikeBreast cancer stromal compartment, may influence responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy (neoCT) in locally advanced breast cancer (LABC). The tumor samples were collected from 44 patients with LABC (29 estrogen receptor (ER) positive and 15 ER negative) before the start of any treatment. Neoadjuvant chemotherapy consisted of doxorubicin and cyclophosphamide, followed by paclitaxel. Response was defined as downstaging to maximum ypT1a-b/ypN0. The stromal cells, mainly composed of fibroblast and immune cells, were microdissected from fresh frozen tumor samples and gene expression profile was determined using Agilent SurePrint G3 Human Gene Expression microarrays. Expression levels were compared using MeV (MultiExperiment Viewer) software, applying SAM (significance analysis of microarrays). To classify samples according to tumor response, the order of median based on confidence statements (MedOr) was used, and to identify gene sets correlated with the phenotype downstaging, gene set enrichment analysis (GSEA). Nine patients presented disease downstaging. Eleven sequences (FDR 17) were differentially expressed, all of which (except H2AFJ) more expressed in responsive tumors, including PTCHD1 and genes involved in abnormal cytotoxic T cell physiology, TOX, LY75, and SH2D1A. The following four pairs of markers could correctly classify all tumor samples according to response: PTCHD1/PDXDC2P, LOC100506731/NEURL4, SH2D1A/ENST00000478672, and TOX/H2AFJ. Gene sets correlated with tumor downstaging (FDR < 0.01) were mainly involved in immune response or lymphocyte activation, including CD47, LCK, NCK1, CD24, CD3E, ZAP70, FOXP3, and CD74, among others. In locally advanced breast cancer, stromal cells may present specific features of immune response that may be associated with chemotherapy response.
- Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis(2015) ENCINAS, Giselly; MAISTRO, Simone; PASINI, Fatima Solange; KATAYAMA, Maria Lucia Hirata; BRENTANI, Maria Mitzi; BOCK, Geertruida Hendrika de; FOLGUEIRA, Maria Aparecida Azevedo KoikeObjective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC) or serous ovarian cancer (SOC). Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of PubMed was performed. Young age for BC and SOC patients was set at <= 35 and <= 40 years, respectively. Age groups were also classified in <30years and every 10 years thereafter. Results: twenty six (1,980 patients, 111 younger) and 16 studies (598, 41 younger), were analyzed for BC and SOC, respectively. In BC, PIK3CA wild type tumor was associated with early onset, not confirmed in binary regression with estrogen receptor (ER) status. In HER2-negative tumors, there was increased frequency of PIK3CA somatic mutation in older age groups; in ER-positive tumors, there was a trend towards an increased frequency of PIK3CA somatic mutation in older age groups. TP53 somatic mutation was described in 20% of tumors from both younger and older patients; PTEN, CDH1 and GATA3 somatic mutation was investigated only in 16 patients and PTEN mutation was detected in one of them. In SOC, TP53 somatic mutation was rather common, detected in more than 50% of tumors, however, more frequently in older patients. Conclusion: frequency of somatic mutations in specific genes was not associated with early-onset breast cancer. Although very common in patients with serous ovarian cancer diagnosed at all ages, TP53 mutation was more frequently detected in older women.
conferenceObject Stromal cell signature in luminal breast cancer associated with response to neoadjuvant chemotherapy.(2018) KATAYAMA, Maria Lucia H.; VIEIRA, Rene A. da Costa; ROELA, Rosimeire A.; ANDRADE, Victor P.; LIMA, Luiz Guilherme C. A. de; ENCINAS, Giselly; KERR, Ligia M.; MAISTRO, Simone; BRENTANI, M. Mitzi; FOLGUEIRA, Maria A. A. Koike- Germline and Somatic mutations in postmenopausal breast cancer patients(2021) NAGY, Tauana Rodrigues; MAISTRO, Simone; ENCINAS, Giselly; KATAYAMA, Maria Lucia Hirata; PEREIRA, Glaucia Fernanda de Lima; GABURO-JUNIOR, Nelson; FRANCO, Lucas Augusto Moyses; GOUVEA, Ana Carolina Ribeiro Chaves de; DIZ, Maria del Pilar Estevez; LEITE, Luiz Antonio Senna; FOLGUEIRA, Maria Aparecida Azevedo KoikeOBJECTIVES: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. METHODS: Forty-nine postmenopausal (>55 years) and forty-one young (<= 35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated. RESULTS: The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations. CONCLUSIONS: Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.
conferenceObject Frequency of CDH1 germline mutations in diffuse gastric cancer in Brazil.(2015) GUINDALINI, Rodrigo Santa Cruz; PASINI, Fatima Solange; GOUVEA, Ana Carolina Ribeiro Chaves De; BRANAS, Priscila Abduch; CORMEDI, Marina Candido Visontai; MAISTRO, Simone; KATAYAMA, Maria Lucia Hirata; ENCINAS, Giselly; NAGY, Tauana; ESTEVEZ-DIZ, Maria Del Pilar; SAFATLE-RIBEIRO, Adriana Vaz; RIBEIRO, Ulysses; FOLGUEIRA, Maria A. A. KoikeconferenceObject Germline BRCA1 and BRCA2 mutations in Brazilian ovarian and breast cancer patients.(2018) MAISTRO, Simone; ENCINAS, Giselly; NAGY, Tauana; TEIXEIRA, Natalia; KATAYAMA, Maria Lucia H.; GOUVEA, Ana Carolina R. C.; DIZ, Maria del Pilar E.; CHAMMAS, Roger; BOCH, Geertruida H. de; FOLGUEIRA, Maria Aparecida A. K.- Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil(2016) MAISTRO, Simone; TEIXEIRA, Natalia; ENCINAS, Giselly; KATAYAMA, Maria Lucia Hirata; NIEWIADONSKI, Vivian Dionisio Tavares; CABRAL, Larissa Garcia; RIBEIRO, Roberto Marques; GABURO JUNIOR, Nelson; GOUVEA, Ana Carolina Ribeiro Chaves de; CARRARO, Dirce Maria; SABINO, Ester Cerdeira; DIZ, Maria del Pilar Estevez; CHAMMAS, Roger; BOCK, Geertruida Hendrika de; FOLGUEIRA, Maria Aparecida Azevedo KoikeBackground: Approximately 8-15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian cancer patients are still lacking. The aim of this study was to evaluate BRCA1/2 mutations, through entire gene sequencing, in a Brazilian population of women with epithelial ovarian cancer. Methods: In a cross sectional study performed in one reference centre for cancer treatment in Sao Paulo, Brazil, 100 patients diagnosed with epithelial ovarian cancer unselected for family history of breast and/or ovarian cancer were included. The complete coding sequence of BRCA1/2 genes was evaluated through Next-Generation or capillary sequencing. Large deletions were investigated through Multiplex Ligation-dependent Probe Amplification (MLPA). Results: Nineteen pathogenic mutations (BRCA1: n = 17 and BRCA2: n = 2) featuring 14 different mutations, including two large deletions in BRCA1 (exon 1-2 deleted and exon 5-7 deleted) were identified. Three mutations were detected more than once (c.3331_3334delCAAG, c.5266dupC and c.4484G > T). Two novel frameshift mutations were identified, one in BRCA1 (c.961_962delTG) and one in BRCA2 (c.1963_1963delC). BRCA1/2 mutations were seen in 35.5% of the patients with first and/or second-degree relatives with breast and/or ovarian cancer. Nineteen variants of uncertain significance (VUS) were detected (BRCA1: n = 2 and BRCA2: n = 17), including five distinct missense variants (BRCA1: c. 5348 T > C; BRCA2: c.2350A > G, c.3515C > T, c.7534C > T, and c.8351G > A). Conclusions: Among epithelial ovarian cancer patients unselected for family history of cancer, 19% were BRCA1/2 germline mutation carriers. Almost 3/4 of the BRCA mutations, including two large deletions, were detected only once. Our work emphasizes the need of entire gene sequencing and MLPA screening in Brazil.
conferenceObject Somatic mutations in Luminal HER2 negative tumors from young breast cancer patients.(2015) ENCINAS, Giselly; ESTEVEZ-DIZ, Maria Del Pilar; LYRA, Eduardo C.; KATAYAMA, Maria Lucia Hirata; PASINI, Fatima Solange; MAISTRO, Simone; SABELNYKOVA, Veronica; BOUTROS, Paul; BRENTANI, Maria Mitzi; BASSO, Ricardo; GOUVEA, Ana Carolina Ribeiro Chaves De; CHAMMAS, Roger; GOES, Joao Carlos Guedes Sampaio; FOLGUEIRA, Maria A. A. Koike- Characterization of risk factors in breast cancer young adult patients(2013) ENCINAS, G.; DIZ, M. D. P. E.; LYRA, E. C.; KATAYAMA, M. L. H.; PASINI, F. S.; BRENTANI, M. M.; CHAMMAS, R.; GOES, J. C. G. S.; FOLGUEIRA, M. A. A. K.