A5044597347- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- Genetic factors in colorectal cancer
- Neuroendocrine Tumor Research Advances
- Breast Lesions and Carcinomas
- Breast Cancer Treatment Studies
- Cancer and Skin Lesions
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Lung Cancer Treatments and Mutations
- Multiple and Secondary Primary Cancers
- Ovarian cancer diagnosis and treatment
- BRCA gene mutations in cancer
- Endometrial and Cervical Cancer Treatments
- Salivary Gland Tumors Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Genomic variations and chromosomal abnormalities
- Pancreatic and Hepatic Oncology Research
- Cancer Diagnosis and Treatment
- Uterine Myomas and Treatments
- Sarcoma Diagnosis and Treatment
- Ear and Head Tumors
- Genomics and Rare Diseases
- Esophageal Cancer Research and Treatment
- Cancer-related molecular mechanisms research
Memorial Sloan Kettering Cancer Center
2016-2025
Kettering University
2022-2024
AC Camargo Hospital
2011
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...
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...
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,...
Lung carcinoids (LC) are rare and slow growing primary lung neuroendocrine tumors. We performed targeted exome sequencing, mRNA DNA methylation array analysis on macro-dissected LCs. Recurrent mutations were enriched for genes involved in covalent histone modification/chromatin remodeling (34.5%; MEN1, ARID1A, KMT2C, KMT2A) as well repair (17.2%) pathways. Unsupervised clustering principle component gene expression profiles showed three robust molecular subtypes (LC1, LC2, LC3) with distinct...
Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Here, we sought to investigate the level intralesion genetic heterogeneity DCIS and patterns clonal architecture changes progression from disease.Synchronous (n = 27) ductal carcinomas no special type (IDC-NSTs; n 26) 25 patients, pure 7) 7 patients were microdissected separately subjected high-depth whole-exome 56) or massively parallel sequencing targeting ≥410 key cancer-related genes 4). Somatic...
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...
Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority patients experience long-term disease control. Using large, clinically annotated cohort with metastatic hormone receptor-positive (HR+) cancer, we identify TP53 loss (27.6%) and MDM2 amplification (6.4%) be associated lack Human cancer models reveal that p53 does not alter activity or G1 blockade but instead promotes drug-insensitive p130 phosphorylation by CDK2. The persistence...
Abstract Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that typically associated with tobacco exposure and inactivation of RB1 TP53 genes. Here, we performed detailed clinicopathologic, genomic, transcriptomic profiling an atypical subset SCLC lacked co-inactivation arose in never/light smokers. We found most cases were chromothripsis—massive, localized chromosome shattering—recurrently involving 11 or 12 resulting extrachromosomal amplification CCND1 co-amplification...
Abstract Sclerosing stromal tumor (SST) of the ovary is a rare type sex cord-stromal (SCST), whose genetic underpinning currently unknown. Here, using whole-exome, targeted capture and RNA-sequencing, we report recurrent FHL2-GLI2 fusion genes in 65% (17/26) SSTs other GLI2 rearrangements additional 15% (4/26) SSTs, none which are detected types SCSTs ( n = 48) or common cancer 9,950). The fusions result transcriptomic activation Sonic Hedgehog (SHH) pathway SSTs. Expression vitro leads to...
Endometrial carcinoma (EC), as described by Bokhman, has historically been classified Type I (low-grade, hormone-dependant, young patients, good prognosis) or II (high-grade, hormone-independent, older poor prognosis). This classification is no longer pragmatic, however, EC a much more heterogeneous disease. Four molecular subtypes of were identified The Cancer Genome Atlas (TCGA), and subsequent studies have demonstrated its utility in predicting prognosis. While endometrial serous (ESC),...
ABSTRACT Acquired genetic alterations commonly drive resistance to endocrine and targeted therapies in metastatic breast cancer 1–7 , however the underlying processes engendering these diverse are largely uncharacterized. To identify mutational operant their impact on clinical outcomes, we utilized a well-annotated cohort of 3,880 patient samples with paired tumor-normal sequencing data. The signatures associated apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3)...
Artificial intelligence (AI) systems can improve cancer diagnosis, yet their development often relies on subjective histologic features as ground truth for training. Herein, we developed an AI model applied to whole-slide images using CDH1 biallelic mutations, pathognomonic invasive lobular carcinoma (ILC) in breast neoplasms, truth. The accurately predicted mutations (accuracy = 0.95) and diagnosed ILC 0.96). A total of 74% samples classified by the having but lacking these alterations...
Abstract Primary pleomorphic adenomas (PAs) and mucoepidermoid carcinomas (MECs) of the breast are vanishingly rare. Here we sought to determine whether PAs MECs would be underpinned by fusion genes reported occur in their salivary gland counterparts. Our study included three one MEC, which were subjected RNA sequencing (PAs, n = 2; 1) or Archer FusionPlex (PA, 1). analyses revealed presence HMGA2 - WIF1 gene PA3, CTNNB1 PLAG1 PA2, CRTC1 MAML2 MEC analyzed (1/1). No oncogenic detected PA1,...
Abstract Mosaic mutations in normal tissues can occur early embryogenesis and be associated with hereditary cancer syndromes when affecting susceptibility genes (CSG). Their contribution to apparently sporadic cancers is currently unknown. Analysis of paired tumor/blood sequencing data 35,310 patients revealed 36 pathogenic mosaic variants CSGs, most which were not detected by prior clinical genetic testing. These CSG consistently at varying variant allelic fractions microdissected (n = 48)...
Triple-negative breast cancers (TNBCs) often have a high Ki-67 proliferation index and respond favorably to neoadjuvant chemotherapy (NACT) with pathologic complete response (pCR) resulting in ~40% of cases. Nevertheless, morbidity/mortality remain high, mostly due recurrence patients residual disease. In contrast, the incidence clinical features TNBC low (TNLP), defined as ≤30% remains unknown. We report 70 cases TNLP identified at our center from 2008 2018, including 18 treated NACT....
Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form neuroendocrine carcinoma, which resembles small lung cancer (SCLC) in its histology poor survival rate. Here, we sought to define genetic underpinning SCCs compare their mutational profiles with those human papillomavirus (HPV)-positive head neck squamous carcinomas, HPV-positive cervical SCLCs using publicly available data. Using combination whole-exome targeted massively parallel sequencing, found that nine...
Abstract Metaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according their histologic subtype. TERT promoter hotspot mutations and gene amplification rare in common forms of cancer, but present a subset phyllodes tumors. Here, we sought determine the frequency genetic alterations affecting cohort 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), compare repertoire presence or...