Gene Mutation That Triggers Colon, Endometrial Cancers Identified

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According to new findings published in the journal Cancer Cell, researchers at the The University of Texas MD Anderson Cancer Center in Houston, Texas, have identified a gene mutation that activates two enzymes that trigger endometrial and colon tumor growth.

 

The PIK3R1 gene has long been known to be involved in the PI3K signaling pathway that plays a role in tumor growth, but the researchers found a new PIK3R1 mutation, a neomorph called R348, that activates extracellular-signal-related kinase (ERK) and c-June N-terminal kinase (JNK) signaling cascades instead of the normal PI3K pathway. Other mutations near R348 also activate these pathways.

 

Data from The Cancer Genome Atlas (TCGA) demonstrates that PIK3R1 gene mutations are one of the most common gene alterations observed in over 20 cancers and is the 12th most commonly mutated gene found in cancer. PIK3R1 gene mutations are particularly common in endometrial and colon cancers. The R348 neomorph prevents cell death by triggering the ERK and JNK signaling cascades, resulting in continued cancer cell proliferation.

 

The researchers suggest that mutation-specific targeted therapy, rather than a treatment targeting the cancer gene, need to be developed to halt tumor growth.

Enzyme May Play Role in DNA Repair, Kidney Cancer
A gene mutation activates two enzymes that trigger endometrial and colon tumor growth.

In the quest to solve cancer's mysteries, they come in handy when describing tongue-twisting processes and pathways that somehow allow tumors to form and thrive. Two examples are ERK (extracellular-signal-related kinase) and JNK (c-June N-Terminal Kinase), enzymes that may offer unexpected solutions for treating some endometrial and colon cancers.

A study led by Gordon Mills, M.D., Ph.D., professor and chair of Systems Biology at The University of Texas MD Anderson Cancer Center with Lydia Cheung, Ph.D. as the first author, points to cellular mutations in the gene PIK3R1 which activate ERK and JNK, thus allowing tumor growth. Results from the study, were published in this month's issue of Cancer Cell.

The PIK3R1 gene has been thought to impact the PI3K pathway since its discovery over two decades ago. The PI3K signaling pathway has long been known to play a role in cancer cell proliferation, and targeting why and how PI3K allows tumor cells to grow has been an important area of study and treatment.

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