Topics

Genomic profiling of the residual disease of advanced high-grade serous ovarian cancer after neoadjuvant chemotherapy.

08:00 EDT 11th October 2019 | BioPortfolio

Summary of "Genomic profiling of the residual disease of advanced high-grade serous ovarian cancer after neoadjuvant chemotherapy."

The goal of this study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre- and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS) (p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC. This article is protected by copyright. All rights reserved.

Affiliation

Journal Details

This article was published in the following journal.

Name: International journal of cancer
ISSN: 1097-0215
Pages:

Links

DeepDyve research library

PubMed Articles [35023 Associated PubMed Articles listed on BioPortfolio]

Targeted Genomic Sequencing Reveals Novel In-frame Deletion Mutations Leading to p53 Overexpression in High-grade Serous Tubo-ovarian Carcinoma.

High-grade serous carcinoma (HGSC) is the most common histological subtype of ovarian carcinoma. Somatic mutation of tumor protein 53 (TP53) is a hallmark of tubo-ovarian HGSC and is observed in almos...

Diagnostic Variation in p53 Usage for Endometrial Carcinoma Diagnosis: Implications for Molecular Subtyping.

Immunostaining for p53 is widely but variably used when diagnosing endometrial carcinoma (EC). Mutant-pattern p53 staining can support a diagnosis of serous carcinoma, and also serve as a surrogate te...

Long-term risk of advanced neoplasia after colonic low-grade dysplasia in patients with inflammatory bowel disease: a nationwide cohort study.

The long-term risk of high-grade dysplasia (HGD) and colorectal cancer (CRC) following low-grade dysplasia (LGD) in inflammatory bowel disease (IBD) patients is relatively unknown. We aimed to determi...

Expression of L1 retrotransposon open reading frame protein 1 (L1ORF1p) in gynecologic cancers.

LINE-1 (L1) retrotransposons are mobile genetic elements capable of "copy-and-pasting" their own sequences into random genomic loci and one of the proteins it uses to achieve mobility is LINE-1 open r...

Platform-Independent Classification System to Predict Molecular Subtypes of High-Grade Serous Ovarian Carcinoma.

Molecular cancer subtyping is an important tool in predicting prognosis and developing novel precision medicine approaches. We developed a novel platform-independent gene expression-based classificati...

Clinical Trials [18034 Associated Clinical Trials listed on BioPortfolio]

Genomic Profiling of the Residual Disease of Advanced-stage Ovarian Cancer After Neoadjuvant Chemotherapy

Tumor response to NAC predicts survival and can be considered a surrogate prognostic marker. Three tiered chemotherapy response score (CRS) of omental tissue sections showed a significant ...

Advanced Cancer Patients Decision Making and Family Communication About Secondary Findings From Tumor Genomic Profiling

The objective of this protocol is to characterize advanced cancer patients' responses to learning their secondary findings arising from tumor genomic profiling, and the process and outcome...

Fulvestrant Plus Palbociclib in Women With Advanced Low Grade Serous Carcinoma

The goal of this clinical research study is to learn if fulvestrant and palbociclib can help to control low-grade serous ovarian cancer. The safety of this drug combination will also be st...

p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246

The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and PLD chemotherapy regimen in patients with platinum-resistant recurrent high grade se...

Trial of Maintenance With Niraparib- Uterine Serous Carcinoma

Uterine serous carcinoma (USC) accounts for up to 40% of endometrial cancer-related deaths. Patients with USC share many genomic and clinical characteristics with patients who has serous o...

Medical and Biotech [MESH] Definitions

A tumor of both low- and high-grade malignancy. The low-grade grow slowly, appear in any age group, and are readily cured by excision. The high-grade behave aggressively, widely infiltrate the salivary gland and produce lymph node and distant metastases. Mucoepidermoid carcinomas account for about 21% of the malignant tumors of the parotid gland and 10% of the sublingual gland. They are the most common malignant tumor of the parotid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575; Holland et al., Cancer Medicine, 3d ed, p1240)

Advanced technology that is costly, requires highly skilled personnel, and is unique in its particular application. Includes innovative, specialized medical/surgical procedures as well as advanced diagnostic and therapeutic equipment.

Pregnancy in which the mother and/or FETUS are at greater than normal risk of MORBIDITY or MORTALITY. Causes include inadequate PRENATAL CARE, previous obstetrical history (ABORTION, SPONTANEOUS), pre-existing maternal disease, pregnancy-induced disease (GESTATIONAL HYPERTENSION), and MULTIPLE PREGNANCY, as well as advanced maternal age above 35.

Neoplasms of the thin serous membrane that envelopes the lungs and lines the thoracic cavity. Pleural neoplasms are exceedingly rare and are usually not diagnosed until they are advanced because in the early stages they produce no symptoms.

A malignant epithelial tumor of glandular tissue, especially the salivary glands, characterized by acini with mucus-producing cells and by the presence of malignant squamous elements. Most mucoepidermoid tumors are low-grade lesions readily cured by adequate excision. They may appear in any age group. They grow slowly. If high-grade, they behave aggressively, widely infiltrating the salivary gland and producing lymph node and distant metastases. (Dorland, 27th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575)

Quick Search


DeepDyve research library

Relevant Topics

Ovarian Cancer
Ovarian Cancer is cancer that starts in the female reproductive organs, the ovaries. It is the fifth most common cancer among women.  Women at risk of Ovarian Cancer are those who have had few children (or had children at an older age), carriers o...

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...


Searches Linking to this Article