A5003635959- Cancer Genomics and Diagnostics
- Breast Cancer Treatment Studies
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- Breast Lesions and Carcinomas
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Cancer and Skin Lesions
- Cancer-related Molecular Pathways
- Salivary Gland Tumors Diagnosis and Treatment
- Cancer Cells and Metastasis
- Multiple and Secondary Primary Cancers
- Cell death mechanisms and regulation
- Gene expression and cancer classification
- Lung Cancer Treatments and Mutations
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Single-cell and spatial transcriptomics
- Genomic variations and chromosomal abnormalities
- Bioinformatics and Genomic Networks
- PI3K/AKT/mTOR signaling in cancer
- Ovarian cancer diagnosis and treatment
- Cancer Treatment and Pharmacology
- Radiomics and Machine Learning in Medical Imaging
- Nuclear Structure and Function
Memorial Sloan Kettering Cancer Center
2016-2025
Kettering University
2017-2024
Imaging Center
2023-2024
University of Turin
2018-2019
Institut Curie
2017-2019
University of Southern California
2019
Candiolo Cancer Institute
2019
University Hospital of Basel
2019
University of Basel
2018
University of Bologna
2018
Abstract High-grade serous ovarian cancer (HGSOC) is an archetypal of genomic instability 1–4 patterned by distinct mutational processes 5,6 , tumour heterogeneity 7–9 and intraperitoneal spread 7,8,10 . Immunotherapies have had limited efficacy in HGSOC 11–13 highlighting unmet need to assess how the anatomical sites foci determine immunological states microenvironment. Here we carried out integrative analysis whole-genome sequencing, single-cell RNA digital histopathology multiplexed...
Purpose: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of cancer, predominantly triple-negative phenotype, characterized by the presence malignant cells showing squamous and/or mesenchymal differentiation. We sought to define repertoire somatic genetic alterations mutational signatures MBCs.Experimental Design: Whole-exome sequencing was performed in 35 MBCs, with 16, 10, 9 classified as harboring chondroid, spindle, metaplasia predominant metaplastic component....
Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative harbor highly recurrent codon Q61 HRAS hotspot which co-occur with PIK3R1 mutations. In two- three-dimensional cell culture models,...
Abstract Granular cell tumors (GCTs) are rare that can arise in multiple anatomical locations, and characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs currently unknown. Here, we apply whole-exome sequencing targeted analysis to reveal mutually exclusive, clonal, inactivating somatic mutations the endosomal pH regulators ATP6AP1 or ATP6AP2 72% GCTs. Silencing these genes vitro results impaired vesicle acidification, redistribution compartments, accumulation...
Abstract Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype an obscure etiology. In this study, we sought to describe its unique histopathologic features and identify the genetic alterations that underpin SPCRP using massively parallel whole-exome targeted sequencing. The morphologic immunohistochemical of support invasive nature subtype. Ten 13 (77%) SPCRPs harbored hotspot mutations at R172 isocitrate dehydrogenase IDH2, which 8 10 displayed concurrent...
Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays role DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics landscape of somatic genetic alterations 24 BCs from ATM mutation carriers by whole-exome targeted sequencing. ATM-associated were consistently hormone receptor positive largely displayed minimal immune infiltrate. Although 79.2% these tumors exhibited loss...
Breast tumors lacking expression of human epidermal growth factor receptor 2 (HER2) and the estrogen progesterone receptors (triple negative; TNBC) are more aggressive than other disease subtypes, no molecular targeted agents currently available for their treatment. Because TNBC commonly displays EGF (EGFR) expression, combinations monoclonal antibodies to EGFR effectively inhibit tumor models, we addressed relevance this strategy treatment TNBC. Unlike a combination clinically approved...
Purpose: Paired primary breast cancers and metachronous metastases after adjuvant treatment are reported to differ in their clonal composition genetic alterations, but it is unclear whether these differences stem from the selective pressures of metastatic process, systemic therapies, or both. We sought define repertoire alterations cancer patients with de novo disease who had not received local therapy.Experimental Design: Up two anatomically distinct core biopsies synchronous distant nine...
BACKGROUND The surgical management of mammary intraductal papilloma without atypia (IDP) identified at core‐needle biopsy (CNB) is controversial. This study assessed the rate upgrade to carcinoma excision (EXC). METHODS women with a CNB diagnosis or cancer center between 2003 and 2013. Radiologic‐pathologic concordance was for all cases, discordant cases were excluded. radiologic clinicopathologic features patients IDP correlated an EXC. RESULTS population consists 189 196 IDPs; 166 (171...
Highlights•In a cohort of >21 000 patients, tumor-only sequencing failed to detect 10.5% pathogenic germline variants in 16 CSGs.•18.8%, 12.8% and 7.3% MMR, DDR HRD genes were not detected by sequencing.•These undetected P/LP may affect the use targeted therapies, preventative measures familial surveillance.•For patients with negative tumor results, genetic testing is needed guide therapy counseling.AbstractBackgroundTumor-only sequencing, implemented for identification somatic variants,...
PURPOSE To determine the genetic predisposition underlying pancreatic acinar cell carcinoma (PACC) and characterize its genomic features. METHODS Both somatic germline analyses were performed using an Food Drug Administration–authorized matched tumor/normal sequencing assay on a clinical cohort of 28,780 patients with cancer, 49 whom diagnosed PACC. For subset PACCs, whole-genome (WGS; n = 12) RNA (n 6) performed. RESULTS Eighteen (36.7%) PACCs harbored pathogenic variants in homologous...
CDH1 (E-cadherin) bi-allelic inactivation is the hallmark alteration of breast invasive lobular carcinoma (ILC), resulting in its discohesive phenotype. A subset ILCs, however, lack genetic/epigenetic inactivation, and their genetic underpinning unknown. Through clinical targeted sequencing data reanalysis 364 primary we identified 25 ILCs lacking alterations. promoter methylation was frequent (63%) these cases. Targeted revealed 3 harboring AXIN2 deleterious fusions (n = 2) or...
Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female tissues, we develop validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, explicitly quantifies intratumoral heterogeneity. Here show mFISHseq has 93% accuracy compared...
Abstract Breast adenoid cystic carcinoma (AdCC), a rare type of triple‐negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned the MYB–NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have reported in – NFIB ‐negative salivary gland AdCCs. Here we report on molecular characterization massively parallel sequencing four AdCCs lacking In two cases, identified rearrangements ( MYBL1–ACTN1 and MYBL1–NFIB ), which were...
Glioblastoma multiforme (GBM) is a highly malignant human brain neoplasm with limited therapeutic options. GBMs display deregulated apoptotic pathway high levels of the antiapoptotic Bcl-2 family proteins and overt activity phosphatidylinositol 3-kinase (PI3K) signaling pathway. Therefore, combined interference PI3K reasonable strategy. ABT-263 (Navitoclax), an orally available small-molecule inhibitor, GDC-0941, were used to treat established glioblastoma neurosphere cells, alone or in...
Mucinous carcinoma of the breast (MCB) is a rare histologic form estrogen receptor (ER)-positive/HER2-negative cancer (BC) characterized by tumor cells floating in lakes mucin. We assessed genomic landscape 32 MCBs whole-exome sequencing and/or RNA-sequencing. GATA3 (23.8%), KMT2C (19.0%), and MAP3K1 (14.3%) were most frequently mutated genes pure MCBs. In addition, two recurrent but not pathognomonic fusion genes, OAZ1-CSNK1G2 RFC4-LPP, detected 3/31 (9.7%) 2/31 (6.5%) samples,...