Detection and genomic characterization of a mammary-like adenocarcinoma

Abstract

Whole-genome and transcriptome sequencing were performed to identify potential therapeutic strategies in the absence of viable treatment options for a patient initially diagnosed with vulvar adenocarcinoma. Genomic events were prioritized by comparison against variant distributions in the TCGA pan-cancer data set and complemented with detailed transcriptome sequencing and copy-number analysis. These findings were considered against published scientific literature in order to evaluate the functional effects of potentially relevant genomic events. Analysis of the transcriptome against a background of 27 TCGA cancer types led to reclassification of the tumor as a primary HER2+ mammary-like adenocarcinoma of the vulva. This revised diagnosis was subsequently confirmed by follow-up immunohistochemistry for a mammary-like adenocarcinoma. The patient was treated with chemotherapy and targeted therapies for HER2+ breast cancer. The detailed pathology and genomic findings of this case are presented herein.

Genome and Transcriptome Biomarkers of Response to Immune Checkpoint Inhibitors in Advanced Solid Tumors

“…PCR-free genomic DNA libraries and poly-A selected RNA libraries were constructed using standard protocols as described previously (Grewal et al, 2017;Jones et al, 2017). Tumour genomes were sequenced to a target depth of 80X coverage and normal peripheral blood samples to 40X coverage with 125 or 150 bp reads on the Illumina (San Diego, California) HiSeq platform.…”

“…Sequences were aligned to human genome version hg19, and single nucleotide variants (SNVs) and insertions and deletions (indels) were called as described in Jones et al, 2017 andGrewal et al, 2017. Structural variants (SVs) were identified followed by merging and annotating using MAVIS (v2.1.1) (Reisle et al, 2019), and filtered for high quality events as described in Pleasance et al (2020). Variants were annotated to genes using SNPEff (v3.2) with the Ensembl database (v69) (Flicek et al, 2014).…”

Primary breast cancer of the vulva with concurrent breast and endometrial cancers: A case report and literature review

“…Management has ranged from radical vulvectomy or wide local excision with adjuvant chemotherapy, radiation, or hormonal therapy; the role of sentinel inguinal lymph node sampling or lymphadenectomy remains unclear (Lopes et al, 2017). A recent case report demonstrated the use of whole-genome and transcriptome sequencing to identify a HER2+ mammary-like vulvar cancer and may provide opportunities for identifying therapeutic options (Grewal et al, 2017).…”

Application of a Neural Network Whole Transcriptome–Based Pan-Cancer Method for Diagnosis of Primary and Metastatic Cancers

“… 25 We demonstrated its application on extensively pretreated metastatic lesions and CUPs. A linear classifier using analysis of variance (ANOVA)–selected features 26 was used to establish the baseline performance for the classifier in the metastatic cohort (eAppendix 1 in the Supplement ). The study was conducted on retrospective data from January 1, 2013, to March 31, 2016, and no follow-up was required.…”