Abstract
BackgroundWe report on a female patient who underwent primary radical resection for a stage 2B Her-2-positive Barrett’s-type esophageal adenocarcinoma (EAC). Despite Her-2 targeted therapy, her disease recurred and required repeated metastectomies.Case presentationDigital cell sorting and targeted sequencing of cancer sub-clones from EAC and metastases revealed a completely mutated TP53, whereas the sorted stromal cells were wild-type. Her-2 amplification was significantly lower in the metastases when the patient became therapy-resistant.ConclusionsThe mechanism of therapy resistance illustrated by this case could only be detected through accurate analysis of tumor sub-populations.Investigating tumor sub-populations of recurrent disease is important for adjusting therapy in recurrent EAC.
Highlights
We report on a female patient who underwent primary radical resection for a stage 2B Her-2-positive Barrett’s-type esophageal adenocarcinoma (EAC)
Investigating tumor sub-populations of recurrent disease is important for adjusting therapy in recurrent EAC
The TP53 mutation was shared by the EAC primary tumor and metastases and we propose that restoring TP53 wild-type activity could be effective for metastases
Summary
Digital cell sorting and omics-technologies in a Barrett’s-type EAC and two metachronous metastases revealed: (1) the true tumor cell mutational status of the somatic mutations and CNVs; (2) a progressive reduction of Her-2 copy-gains in the two recurrent metastases compared to the primary tumor, not detectable by ISH. We demonstrated that a genomic dissection of EAC and recurrent metastases could identify the tumor cell mutational status, as in this case for a TP53 mutation and Her copy-gains. A WES approach in unsorted material could identify additional CNVs in the different samples, but not the true tumor cell mutational status. A 18 Mb region on chromosome 6 (q21-22.33) is indicated (red box), where CNV analysis identified a copy gain in PT (A) and M1 (B), as reported in Additional file 1: Table S2.
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