Desmoid Tumors: An Extended Diagnostic Panel

Matthew Zamora
Richard Conroy
Anubrata Das
Paul Zamora
For general audience. Detailed paper available upon request.


Problem Statement

A patient case was presented that did not match canonical genetic mutations for Desmoid Tumors, namely either a mutation to either CTNNB1 and APC genes. Alternative biological pathway and mechanisms are explored, with an emphasis on useful tests, and therapies.

Basic Solution

We present a panel of extended tests for alternative biological pathways that may cause Desmoid Tumors, beyond the canonical mutations of CTNNB1 and APC. This extended testing panel may provide insights for alternate therapies for those with Desmoid Tumors that do not have obvious mutations.

Panel Overview Solution

Literature review, and putative genetic network analysis was performed to review possible mechanisms with targetable therapy alternatives. Presented is a test assay sequence, beyond traditional testing such as:

a) β-Catenin Mutation Analysis
b) GEM ExTra® test
c) FISH, Fluorescent In Situ Hybridization (for EGFR and CO1A1)
d) MSK-Isabl Whole Genome Report
e) MSK-Impact

We propose a set of tests in support of alternate disease pathways, and propose potential therapies for each potential pathway. Oncogene pathways we highlight as possibly relevant to Desmoid Tumors include:

  1. PI3k/ATK/mTOR pathway
  2. Raf/RAS/MAPK pathway
  3. Notch pathway
  4. Estrogen receptor pathway
  5. KIT receptor pathway

These pathways are alternatives to the canonical Wnt/β-catenin signaling pathway [4]. Also not discussed is Hedgehog, JAK/STAT which are not believed to have good drug targets at the time of this project.

Project Details


The patient is a 35-year-old female, who presented with a mass on the back, had no reported history of trauma, surgery, childbearing, or history of FAP (Familial Polyposis). A biopsy was used to establish the histological diagnosis of DT. The patient with active DT disease (11 years) arising from the muscle wall of the back (thorax).

The treatments used with the patient so far are consistent with generally recognized treatment options for DTs [9]. The patient has undergone several non-drug therapeutic interventions including surgery, high intensity ultrasound, and radiation therapy. The patient also underwent pharmacologic treatment with NSAIDS (Sulindac), Sorafenib, Doxil, and Methotrexate/vinorelbine. In the medical literature, Doxil (liposomal doxorubicin) and Methotrexate/vinorelbine are each reportedly useful in the treatment of DF [6-8]. Sorafenib is a tyrosine kinase inhibitor that has been reported in phase III trial to be useful in treating DTs [10] with up to one third of patients having tumor regression. The tumor responded to low dose Sorafenib, but high dose Sorafenib was not tolerated by the patient. The tumor also responded to Doxil. Methotrexate/vinorelbine was not effective. Anti-hormonal therapy has not been used.



For the patient no therapeutic intervention tried to date has provided a lasting solution. A review of the genetic testing information available to date has not pointed to a clear therapeutic option. The genetic testing has however provided a platform which with additional testing may provide a clearer therapeutic direction. The additional testing falls under two modes:

a) Immunohistochemistry (IHC) for specific protein domains (antigens) or
b) Real-time reverse transcription polymerase chain reaction (RT-qPCR) for mRNA.

The purpose of the testing is to identify the tumor cell signaling pathway likely to be the most responsive to therapy and to provide pharmacologic suggestions based on testing outcomes. The testing will be complimentary to the genetic testing and will not duplicate it. The outcomes from the testing and recommendations will be presented by pathway as outlined below for:

  1. PI3k/ATK/mTOR
    1. Phosphorylated ATK
    2. Phosphorylated S6K
  2. Raf/RAS/MAPK pathway
    1. HRAS
    2. p-Erk1/ERK2
  3. Notch pathway
    1. Notch intracellular domain (NICD) neoepitope
    2. Hes1
  4. Estrogen receptor pathway
    1. Estrogen receptor-α
    2. Estrogen receptor-β
    3. Progesterone receptor
  5. Kit pathway
    1. KIT
    2. Stem Cell Factor (SCF)
  6. Wnt/β-Catenin pathway (canonical pathway)
    1. nuclear located β-Catenin
    2. cytoplasm stain for β-Catenin
    3. CTNNB1 or APC mutation


Future Directions

  1. Mid-Term – Validating Alternatives – Testing/Assays
  2. Long Term – Generating a Case Report for this patient, since they are in a unique class of patient where conventional genetic mutations are not present
  3. Very Long Term - Generalizing the testing and assay process to support therapy selection for those with non-typical DT mutations