Introduction And Objective: Unlike clear cell renal cell carcinoma (CCRCC), collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare tumors that progress rapidly and appear resistant to current systemic therapies. We queried comprehensive genomic profiling to uncover opportunities for targeted therapy and immunotherapy.
Material And Methods: DNA was extracted from 40 microns of formalin-fixed, paraffin-embedded specimen from relapsed, mCDC (n = 46), mRMC (n = 24), and refractory and metastatic (m) mCCRCC (n = 626).
Background: In patients with rare histologies of bladder cancer, including adenocarcinoma of the bladder (ACB) and squamous-cell carcinoma (SCC), there are limited standard therapy options, defining an unmet medical need.
Objective: In this comparative comprehensive genomic profiling (CGP) study, genomic alterations (GAs), and immuno-oncology (IO) biomarkers have been analyzed.
Design, Setting, And Participants: Within the Foundation Medicine database, 143 cases with centrally reviewed pure ACB, 2142 with pure urothelial carcinoma (UC), and 83 with pure SCC were subjected to CGP.
Purpose: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable.
View Article and Find Full Text PDFBackground: Metastatic testicular sex cord stromal tumors of the testis (MSCSTs) comprise an extremely uncommon form of genitourinary malignancy.
Objective: To perform comprehensive genomic profiling (CGP) to enable the search for potential therapy targets.
Design, Setting, And Participants: Ten patients with testicular Leydig cell tumors (LCTs), six with Sertoli cell tumors (SCTs), and three with undifferentiated sex cord stromal tumors (USCSTs) and a comparison group of 366 patients with ovarian sex cord stromal tumors (SCSTs) underwent hybrid-capture-based CGP to evaluate all classes of genomic alterations (GAs).
Objective: Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially aromatase inhibitors (AIs). The purpose of this study was to evaluate the frequency and clinical relevance of ESR1 genomic alterations in gynecologic malignancies.
View Article and Find Full Text PDFPrimary mediastinal nonseminomatous germ cell tumors (PMNSGCT) frequently become refractory to chemotherapy, and no effective salvage therapy exists. We performed genomic profiling on a series of 44 PMNSGCT and compared the results with those from chemorefractory, metastatic pure seminomatous (Sem, = 22) and nonseminomatous (NS, = 86) testicular germ cell tumors. Archival tissues were sequenced by a hybrid capture-based technology (FoundationONE; Foundation Medicine, Inc.
View Article and Find Full Text PDFFusions involving the oncogenic gene RET have been observed in thyroid and lung cancers. Here we report RET gene alterations, including amplification, missense mutations, known fusions, novel fusions, and rearrangements in breast cancer. Their frequency, oncogenic potential, and actionability in breast cancer are described.
View Article and Find Full Text PDFPurpose: Metastatic penile squamous cell carcinoma is an aggressive malignancy with limited treatment options. We compared the potential therapy impacting genomic alterations between metastatic penile squamous cell carcinoma and nonpenile metastatic cutaneous squamous cell carcinoma.
Materials And Methods: DNA was extracted from 40 μ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma.
BCR-ABL1-like B-Acute Lymphoblastic Leukemia (B-ALL) is a subset of B-ALL with a poor prognosis that is found in all age groups. Definitive identification of these patients is difficult in routine clinical practice as gene expression profiling, the gold standard test, is not widely available. Comprehensive genomic profiling performed on 450 patients with extensive fusion profiling revealed a wide range of genomic alterations which were consistent with a classification of BCR-ABL1-like B-ALL in 29% of cases.
View Article and Find Full Text PDFBackground: Although both seminomatous and nonseminomatous testicular germ cell tumors (TGCTs) have favorable outcomes with chemotherapy, a subset is chemorefractory, and novel therapeutic options are needed.
Objective: To molecularly characterize chemotherapy-refractory TGCTs.
Design, Setting, And Participants: Archival tissues from 107 chemotherapy-treated and relapsed TGCT patients (23 seminomas; 84 nonseminomas) underwent hybrid-capture-based genomic profiling to evaluate four classes of genomic alterations (GAs).
The Mycobacterium tuberculosis ATP-binding cassette transporter Rv1747 is a putative exporter of cell wall biosynthesis intermediates. Rv1747 has a cytoplasmic regulatory module consisting of two pThr-interacting Forkhead-associated (FHA) domains connected by a conformationally disordered linker with two phospho-acceptor threonines (pThr). The structures of FHA-1 and FHA-2 were determined by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, respectively.
View Article and Find Full Text PDFTo define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance. The genetic profiles of 583 advanced differentiated and 196 ATCs generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed. ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared with other thyroid cancer types.
View Article and Find Full Text PDFBackground: In our recent study, of cases positive for epidermal growth factor receptor () exon 19 deletions using comprehensive genomic profiling (CGP), 17/77 (22%) patients with prior standard of care (SOC) testing results available were previously negative for exon 19 deletion. Our aim was to compare the detection rates of CGP versus SOC testing for well-characterized sensitizing point mutations (pm) in our 6,832-patient cohort.
Materials And Methods: DNA was extracted from 40 microns of formalin-fixed paraffin-embedded sections from 6,832 consecutive cases of non-small cell lung cancer (NSCLC) of various histologies (2012-2015).
Background: In contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted therapies.
View Article and Find Full Text PDFObjective: Small cell carcinoma of the ovary, hypercalcemic-type (SCCOHT) is a rare, extremely aggressive neoplasm that usually occurs in young women and is characterized by deleterious germline or somatic SMARCA4 mutations. We performed comprehensive genomic profiling (CGP) to potentially identify additional clinically and pathophysiologically relevant genomic alterations in SCCOHT.
Methods: CGP assessment of all classes of coding alterations in up to 406 genes commonly altered in cancer and intronic regions for up to 31 genes commonly rearranged in cancer was performed on 18 SCCOHT cases (16 exhibiting classic morphology and 2 cases exhibiting exclusive a large cell variant morphology).
Background: Genomic fusions of the anaplastic lymphoma kinase gene () are a well-established therapy target in non-small cell lung cancer (NSCLC). From a survey of 114,200 clinical cases, we determined the prevalence of rearrangements (r) in non-NSCLC tumors and report their responsiveness to therapies targeting ALK.
Materials And Methods: Comprehensive genomic profiling of 114,200 relapsed and metastatic malignancies, including both solid tumors and hematolymphoid cancers, was performed using a hybrid-capture, adaptor ligation-based next-generation sequencing assay.
Hepatoblastoma (HBL) is a hepatic malignancy of infants and young children, which is often cured by combinations of surgery and chemotherapy. Management of refractory and metastatic HBL is challenging. Comprehensive genomic profiling was performed on 31 refractory and metastatic HBL using a hybrid-capture, adaptor ligation-based next-generation sequencing assay.
View Article and Find Full Text PDF•We report an ovarian cancer patient with a prolonged response to immunotherapy.•Comprehensive genomic profiling may detect patients who benefit from immunotherapy.•Mutational burden thresholds for ovarian cancer may be lower than other cancers.
View Article and Find Full Text PDFGynecol Oncol Rep
August 2017
•Secondary, reversion mutations in genes can restore protein function.•Reversion mutations can underlie resistance to therapies such as PARP inhibitors.•Reversion mutations arise during the course of treatment.
View Article and Find Full Text PDFEnzymatic conversion of chitin, a β-1,4 linked polymer of N-acetylglucosamine, is of major interest in areas varying from the biorefining of chitin-rich waste streams to understanding how medically relevant fungi remodel their chitin-containing cell walls. Although numerous chitinolytic enzymes have been studied in detail, relatively little is known about enzymes capable of deacetylating chitin. We describe the structural and functional characterization of a 237 residue deacetylase (AnCDA) from Aspergillus nidulans FGSC A4.
View Article and Find Full Text PDFBackground: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit.
View Article and Find Full Text PDF•MTOR pathway genes are often mutated in ovarian clear cell carcinomas (OCCC).•11.2% of OCCC have targetable alterations only in the mTOR pathway.
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