Publications by authors named "Quintanilha J"

Article Synopsis
  • The study analyzes the genomic differences between early-stage (1-3) and late-stage (IV) colorectal cancer (CRC), finding that early-stage patients show unique genomic alterations, particularly higher rates of microsatellite instability (MSI) and tumor mutational burden (TMB).
  • Data was collected from over 4,700 patients through a clinico-genomic database, revealing that 546 early-stage patients experienced recurrence within one year, often with different genomic profiles compared to later-stage patients.
  • The findings suggest that comprehensive genomic profiling (CGP) can identify distinct characteristics in early-stage CRC patients and enhance their access to targeted therapies, which are more frequently administered when CGP is conducted prior to first-line treatment.
View Article and Find Full Text PDF

Microsatellite instability high (MSI-H) and mismatch repair deficient (dMMR) tumor status have been demonstrated to predict patient response to immunotherapies. We developed and validated a next-generation sequencing (NGS)-based companion diagnostic (CDx) to detect MSI-H solid tumors via a comprehensive genomic profiling (CGP) assay, FoundationOne®CDx (F1CDx). To determine MSI status, F1CDx calculates the fraction of unstable microsatellite loci across >2000 loci using a fraction-based (FB) analysis.

View Article and Find Full Text PDF

Background: Controlled trials have consistently demonstrated the efficacy of poly(ADP-ribose) polymerase inhibitors (PARPis) in patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1 or BRCA2 alterations (BRCAalt). However, the reported efficacy of PARPi for alterations in other homologous recombination repair (HRR) genes is less consistent. We sought to evaluate the routine practice effectiveness of PARPi between and within these groups.

View Article and Find Full Text PDF

Purpose: The purpose of the study was to compare the effectiveness of PARP inhibitor maintenance therapy (mPARPi) in real-world practice by biomarker status [BRCA1/2 alterations (BRCAalt) and a homologous recombination deficiency signature (HRDsig)] in advanced ovarian cancer.

Experimental Design: Patients with ovarian cancer receiving first-line platinum-based chemotherapy and either mPARPi or no maintenance were included. Patient data were obtained by a US-based de-identified ovarian cancer Clinico-Genomic Database, from ∼280 US cancer clinics (01/2015-03/2023).

View Article and Find Full Text PDF
Article Synopsis
  • Bevacizumab, a cancer treatment, can cause hypertension, presenting a challenge in patient care and highlighting the need for better safety measures.
  • This study looked at specific biomarkers—lower levels of VEGF-A, angiopoietin-2, and a genetic variation (rs6770663 in KCNAB1)—to determine their role in predicting high blood pressure in cancer patients receiving this drug.
  • The findings showed that these biomarkers are independently linked to increased risk of hypertension, and combining them can enhance prediction accuracy for patients at risk.
View Article and Find Full Text PDF

Background: The treatment landscape for HR(+)HER2(-) metastatic breast cancer (MBC) is evolving for patients with ESR1 mutations (mut) and PI3K/AKT pathway genomic alterations (GA). We sought to inform clinical utility for comprehensive genomic profiling (CGP) using tissue (TBx) and liquid biopsies (LBx) in HR(+)HER2(-) MBC.

Methods: Records from a de-identified breast cancer clinicogenomic database for patients who underwent TBx/LBx testing at Foundation Medicine during routine clinical care at ~ 280 US cancer clinics between 01/2011 and 09/2023 were assessed.

View Article and Find Full Text PDF

Background: Dengue, Zika, and chikungunya, whose viruses are transmitted mainly by Aedes aegypti, significantly impact human health worldwide. Despite the recent development of promising vaccines against the dengue virus, controlling these arbovirus diseases still depends on mosquito surveillance and control. Nonetheless, several studies have shown that these measures are not sufficiently effective or ineffective.

View Article and Find Full Text PDF

Background: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms.

View Article and Find Full Text PDF

Purpose: Recent studies have provided evidence for a predictive value of genetic alterations (GAs) as biomarkers for targeted therapies in microsatellite-stable (MSS) colorectal cancer (CRC). These data have the potential to prioritize treatment strategies in patients with -mutant CRC and help to identify a subgroup that is more likely to derive benefit versus those patients for whom alternative treatment approaches are needed. We were therefore interested in defining the precise frequency of and GAs and their respective overlap in a large cohort of patients with CRC.

View Article and Find Full Text PDF

Purpose: ERBB2-amplified colorectal cancer is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic RAS/RAF alterations are not known.

Experimental Design: Dana-Farber and Foundation Medicine Inc.

View Article and Find Full Text PDF

Congenital Zika syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation.

View Article and Find Full Text PDF
Article Synopsis
  • This study identified protein quantitative trait loci (pQTL) related to angiogenic and inflammatory proteins in patients with metastatic colorectal cancer (mCRC) using genetic and protein data from a large clinical trial.
  • The analysis revealed a new pQTL associated with TGF-2 protein levels, validated in additional cancer patient datasets, and confirmed previously reported associations with VEGF-A and other protein markers.
  • The findings enhance our understanding of how genetic variants influence protein levels in mCRC, potentially guiding future cancer treatments and research.
View Article and Find Full Text PDF

The standard treatment for head and neck squamous cell carcinoma (HNSCC) is cisplatin chemoradiotherapy. One of the main treatment adverse reactions is nephrotoxicity, for which there is currently no adequate specific and sensitive biomarker. Thus, this study aimed to evaluate the use of microRNAs (miRNAs) as renal biomarker candidates.

View Article and Find Full Text PDF

Purpose: Genomic rearrangements can generate potent oncogenic drivers or disrupt tumor suppressor genes. This study examines the landscape of fusions and rearrangements detected by liquid biopsy (LBx) of circulating tumor DNA (ctDNA) across different cancer types.

Experimental Design: LBx from 53,842 patients with 66 solid tumor types were profiled using FoundationOneLiquid CDx, a hybrid-capture sequencing platform that queries 324 cancer-related genes.

View Article and Find Full Text PDF

Unlabelled: Tumor mutational burden (TMB) is a biomarker that predicts response to immune checkpoint inhibitor therapy. We currently lack a comprehensive understanding of how genomic and clinical factors correlate with TMB. We used a clinicogenomic database to assess independent predictors of TMB levels.

View Article and Find Full Text PDF

The microRNA (miRNA) expression profile by qRT-PCR depends directly on the most appropriate normalization strategy adopted; however, currently there is no universally adequate reference gene. Therefore, this study aimed to determine, considering RNA-Seq results, the most adequate endogenous normalizer for use in the relative quantification of urine miRNAs from head and neck cancer patients, treated with cisplatin chemoradiotherapy. The massive sequencing was performed to identify the miRNAs differentially expressed between the group with cisplatin nephrotoxicity ( = 6) and the one without ( = 6).

View Article and Find Full Text PDF
Article Synopsis
  • PDAC is typically nonimmunogenic, but about 1% of patients exhibit high tumor mutational burden (TMB) or other alterations that could indicate a better response to immune checkpoint inhibitors (ICI).
  • In a study of 21,932 PDAC patients, only 1.3% showed high-TMB, with associated genomic alterations differing based on TMB levels.
  • Patients with high-TMB who received ICI therapy had significantly improved overall survival compared to those with low-TMB, highlighting the potential of high-TMB as a biomarker for ICI therapy efficacy in PDAC.
View Article and Find Full Text PDF

Oxaliplatin (OXAL) is a commonly used chemotherapy for treating colorectal cancer (CRC). A recent genome wide association study (GWAS) showed that a genetic variant (rs11006706) in the lncRNA gene and partnered sense gene could impact the response of genetically varied cell lines to OXAL treatment. This study found that the expression levels of and in lymphocytes (LCLs) and CRC cell lines differed between the rs11006706 genotypes, indicating that this gene pair could play a role in OXAL response.

View Article and Find Full Text PDF

Temozolomide (TMZ) chemotherapy is an important tool in the treatment of glioma brain tumors. However, variable patient response and chemo-resistance remain exceptionally challenging. Our previous genome-wide association study (GWAS) identified a suggestively significant association of SNP rs4470517 in the (receptor-like kinase) gene with TMZ drug response.

View Article and Find Full Text PDF

Anti-BRAF/EGFR therapy is approved for metastatic colorectal cancer (mCRC) with BRAFV600E mutations, although not all patients respond. Novel recent findings indicate the potential of RNF43 mutations to predict outcomes in patients with BRAF-mutated microsatellite stable (MSS) mCRC treated with anti-BRAF/EGFR therapy. This study aimed to independently and rapidly validate BRAFV600E/RNF43 co-mutations as predictive biomarkers of benefit to anti-EGFR/BRAF therapy.

View Article and Find Full Text PDF

Objective: Molecular profiling is developing to inform treatment in endometrial cancer. Using real world evidence, we sought to evaluate frontline immune checkpoint inhibitor vs chemotherapy effectiveness in advanced endometrial cancer, stratified by Tumor Mutational Burden (TMB) ≥10 mut/MB and microsatellite instability (MSI).

Methods: Patients with advanced endometrial cancer in the US-based de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database were included.

View Article and Find Full Text PDF

Importance: The KEYNOTE-177 trial demonstrated that patients with metastatic colorectal cancer (MCRC) with high microsatellite instability (MSI-H) and/or mismatch repair deficiency (DMMR) have better outcomes when receiving first-line immune checkpoint inhibitors (ICIs) compared with chemotherapy. Data on performance of ICIs in patients with MCRC in standard practice settings remain limited, and direct MMR vs MSI outcome association comparisons are lacking.

Objective: To validate MSI (determined by next-generation sequencing [NGS]) as a biomarker of ICI effectiveness among patients with MCRC in standard practice settings and examine the association of MSI assessed by NGS, DMMR by immunohistochemistry, and tumor mutational burden (cutoff, 10 mutations/megabase) with ICI outcomes.

View Article and Find Full Text PDF

Cisplatin is associated with dose-limiting nephrotoxicity, and the timely detection of acute kidney injury (AKI) can affect morbimortality. Therefore, this study aimed to investigate the tools for monitoring renal function in AKI. This was a retrospective, cohort study.

View Article and Find Full Text PDF

The construction and expansion of roads cause significant impacts on the environment. The main potential impacts to biotic environment are vegetation suppression, reduction of the amount and composition of animal distribution due to forest fragmentation and increasing risks of animal (domestic and wildlife) vehicle collisions. The objective of this work was to establish a relationship between the different spatial patterns in wildlife-vehicle crash, by using spatial analysis and machine learning tools.

View Article and Find Full Text PDF