Locations:
Search IconSearch
October 3, 2019/Cancer

Predicting Cancer Versus Autism Risk in Patients With PTEN Mutations

Biomarker may help individualize treatment

Genetic research

In a new study published in American Journal of Human Genetics, a team of researchers led by Charis Eng, MD, PhD, Chair of Cleveland Clinic’s Genomic Medicine Institute, identified a metabolite that may predict whether individuals with PTEN mutations will develop cancer or autism spectrum disorder (ASD).

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Germline mutations of the tumor suppressor gene PTEN are associated with a spectrum of rare genetic disorders that increase the risk of certain cancers, cognitive and behavioral deficits, benign growths and tumors (i.e., hamartomas) and macrocephaly. These disorders are referred to collectively as PTEN hamartoma tumor syndrome (PHTS), but clinical manifestations vary greatly among patients and often are difficult to anticipate.

For example, subsets of Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS), two well-defined disorders on the PHTS spectrum, are characterized by either a high risk of certain cancers or ASD. There are functional and structural differences between PTEN mutations associated with ASD and those associated with cancer. However, a biomarker that could proactively determine if a patient with CS/BRRS will develop cancer or ASD has not yet been identified.

Previous studies have established metabolic dysregulation as one of the hallmarks of cancer. Specifically, germline variants in the SDHx genes cause an accumulation of the metabolite succinate, which has been linked to tumorigenesis. Some patients with PTEN mutations have been found to have succinate accumulation despite the lack of SDHx mutations, suggesting that variations in metabolite levels may indicate susceptibility to cancer versus ASD.

A potential biomarker

To investigate this further, Dr. Eng’s team analyzed the metabolite levels of 511 patients with CS, BRRS, or Cowden-like syndrome compared to controls. The results suggest that certain metabolites are associated with specific mutations and/or clinical features.

Advertisement

In particular, they discovered that decreased levels of fumarate, a metabolite formed from succinate, was more strongly associated with ASD or other developmental disorders compared to cancer in individuals with PTEN mutations. These findings indicate that certain metabolites, such as fumarate, may serve as predictive biomarkers that could distinguish patients who will develop neurodevelopmental disorders from those who will develop cancer.

“By identifying a way to differentiate those with germline PTEN mutations who develop cancer and those who develop autism, this provides clinicians with a new tool to better tailor treatments to individual patients,” says Dr. Eng.

Note: This article was originally published here.

Advertisement

Related Articles

Photonic sensor
May 22, 2025/Cancer/News & Insight
Novel Partnership Aims to Advance ctDNA Testing in Non-Small Cell Lung Cancer

Cleveland Clinic, the University of Minnesota and University of Cambridge receive $1M grant to develop point-of-care biosensor for early detection and treatment personalization

gastroesophageal cancer illustration
May 20, 2025/Cancer/News & Insight
Roughly One-Third of Patients with Metastatic Gastroesophageal Cancer May be Eligible for New Targeted Therapy

Long-acting antiemetics and high-dose steroids key to minimizing acute nausea

Neoadjuvant immunotherapy
May 16, 2025/Cancer/News & Insight
Changing Course in Treating Advanced Melanoma

Neoadjuvant immunotherapy improves outcomes

Dr. Abhay Singh
May 14, 2025/Cancer
Managing Weight and Diabetes May Offer Promise for Blood Cancer Prevention (Podcast)

Use of GLP-1s and improving cardiovascular health lowers risk of hematologic malignancies

Oncologist consulting with couple
April 29, 2025/Cancer/News & Insight
Are Your Patients With Cancer Experiencing Sexual Dysfunction? Just Ask!

Sexual disorders affect patients across all cancer types

Dr. Khorana
April 25, 2025/Cancer/News & Insight
Molecular Insights into Early-Onset Biliary Tract Cancer (Podcast)

A call for awareness about the importance of genomic testing

Dr. Melenhorst
April 24, 2025/Cancer/News & Insight
Explore Developments in CAR T-Cell Therapy for CLL (Podcast)

Discussing research into improving CAR T-cell therapy efficacy

Dr. Cherian
April 23, 2025/Cancer/News & Insight
De-intensifying Radiation Therapy in Low-Risk Breast Cancer

Ultra-Hypofractionated Whole Breast Irradiation and Partial Breast Irradiation Reduce Many Toxicities

Ad