Illustration of a DNA helix blossoming into a flower, symbolizing hope and scientific progress in colorectal cancer treatment.

Decoding Cancer's Code: How Frameshift Mutations in Specific Genes Could Change Colorectal Cancer Treatment

Kai Mendoza in Health & Wellness December 2025 • 5 min read.

"New research uncovers how specific gene mutations might hold the key to better understanding and treating colorectal cancer."

Colorectal cancer (CRC), a significant global health concern, affects millions annually. While treatment options have improved, the disease's complexity demands a deeper understanding of its underlying mechanisms. Recent research has illuminated the role of specific genetic mutations in CRC, offering a new perspective on how these alterations impact the disease's progression and potential treatment strategies.

This article delves into a study that examines frameshift mutations in several genes within CRC. These mutations, occurring in genes like ANK3, HACD4, TP53BP1, and others, could play a crucial role in the development and behavior of these cancers. By understanding the impact of these mutations, researchers hope to improve diagnostic methods and develop more effective treatments.

The implications of this research extend beyond the lab, potentially affecting patient care and treatment approaches. This article will explore the study's findings, their significance, and how they might influence future directions in CRC management, offering hope for improved outcomes for those affected by this challenging disease.

The Genetic Landscape of Colorectal Cancer: Unraveling Frameshift Mutations

Illustration of a DNA helix blossoming into a flower, symbolizing hope and scientific progress in colorectal cancer treatment.

The study, published in the journal Pathol. Oncol. Res., focused on frameshift mutations—genetic alterations that disrupt the reading frame of a gene, leading to potentially non-functional proteins. Researchers investigated these mutations in a set of genes, including ANK3, HACD4, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8, and METTL16. These genes were selected due to their involvement in various cellular processes and their potential roles in cancer development.

The research team analyzed 124 cases of colorectal cancer, focusing on tumors with high microsatellite instability (MSI-H), a characteristic often associated with frameshift mutations. They found that several genes harbored these mutations, with ANK3, HACD4, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8, and METTL16 all showing evidence of frameshift mutations. The study also revealed the presence of intratumoral heterogeneity (ITH), meaning that different regions within the same tumor could have varying mutation profiles.

ANK3: This gene is involved in cell survival. Frameshift mutations in ANK3 were found in 13.9% of the MSI-H tumors.
HACD4: Associated with fatty acid synthesis. Mutations were present in 3.8% of the MSI-H tumors.
TP53BP1: This gene interacts with the p53 protein and functions as a tumor suppressor. Frameshift mutations were identified in 6.3% of the MSI-H tumors.
MFN1: Encodes a mitochondrial membrane protein and is also considered a tumor suppressor. Mutations occurred in 1.3% of the MSI-H tumors.
Other Genes: LCMT2, RNMT, TRMT6, METTL8, and METTL16 also showed mutations, though at varying frequencies.

These findings suggest that frameshift mutations in these genes could play a significant role in the development and progression of CRC, particularly in tumors with MSI-H. The presence of ITH further complicates the picture, highlighting the need for a more nuanced understanding of how these mutations impact the disease's behavior and response to treatment. The research opens the door to further investigation into the functional consequences of these mutations and their potential as therapeutic targets.

Looking Ahead: The Future of Colorectal Cancer Treatment

This research offers valuable insights into the genetic complexities of CRC, potentially paving the way for personalized treatment strategies. As scientists continue to decode the genetic landscape of cancer, the hope is that these findings will lead to more effective therapies and improved outcomes for individuals affected by this disease. Further research, including larger studies and functional analyses, is crucial to validate these findings and translate them into clinical practice. The journey to conquer cancer is ongoing, and each scientific discovery brings us closer to a future where this disease is more manageable and treatable.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1007/s12253-017-0287-2, Alternate LINK

Title: Frameshift Mutations In Repeat Sequences Of Ank3, Hacd4, Tcp10L, Tp53Bp1, Mfn1, Lcmt2, Rnmt, Trmt6, Mettl8 And Mettl16 Genes In Colon Cancers

Subject: Cancer Research

Journal: Pathology & Oncology Research

Publisher: Springer Science and Business Media LLC

Authors: Su Yeon Yeon, Yun Sol Jo, Eun Ji Choi, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee

Published: 2017-08-12

Everything You Need To Know

What are frameshift mutations, and why are they important in colorectal cancer research?

Frameshift mutations are genetic alterations that disrupt the reading frame of a gene, potentially leading to non-functional proteins. In colorectal cancer research, these mutations are crucial because they can significantly impact the development and progression of the disease. Genes like ANK3, HACD4, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8, and METTL16, which are involved in various cellular processes, have been found to harbor frameshift mutations in colorectal cancer tumors. Understanding these mutations may improve diagnostic methods and lead to more effective, targeted treatments.

Which specific genes are most frequently affected by frameshift mutations in colorectal cancer tumors with high microsatellite instability (MSI-H)?

In colorectal cancer tumors characterized by high microsatellite instability (MSI-H), genes such as ANK3, HACD4, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8, and METTL16 have been identified with frameshift mutations. Specifically, ANK3 mutations were found in 13.9% of MSI-H tumors, HACD4 in 3.8%, and TP53BP1 in 6.3%. MFN1 showed mutations in 1.3% of these tumors. While LCMT2, RNMT, TRMT6, METTL8, and METTL16 also showed mutations, they occurred at varying frequencies. The identification of these mutations in these specific genes is significant for understanding the genetic underpinnings of colorectal cancer.

How does intratumoral heterogeneity (ITH) complicate the treatment of colorectal cancer, and how does it relate to frameshift mutations?

Intratumoral heterogeneity (ITH) refers to the presence of different genetic mutation profiles within different regions of the same tumor. This complicates colorectal cancer treatment because a single treatment approach may not be effective for all areas of the tumor. The study revealed that frameshift mutations in genes like ANK3, HACD4, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8, and METTL16 can vary across different regions within the same tumor. This means that some areas might respond to a specific therapy targeting one mutation, while other areas with different mutations might not respond, or even develop resistance. Understanding ITH is crucial for developing more personalized and effective treatment strategies.

What are the potential implications of identifying frameshift mutations in genes like ANK3, HACD4, and TP53BP1 for future colorectal cancer treatments?

Identifying frameshift mutations in genes like ANK3, HACD4, and TP53BP1 holds significant potential for future colorectal cancer treatments. ANK3, involved in cell survival, HACD4, associated with fatty acid synthesis and TP53BP1, which interacts with the p53 protein and functions as a tumor suppressor, all have frameshift mutations, in MSI-H tumors. These mutations can be targeted using personalized treatment strategies that are tailored to the specific genetic makeup of a patient's tumor. For instance, drugs could be developed to specifically target cells with ANK3 mutations, while others could focus on HACD4 or TP53BP1 mutations. Furthermore, understanding these mutations can help in developing diagnostic tools to identify patients who are more likely to benefit from targeted therapies, leading to improved outcomes and more effective cancer management.

Beyond ANK3, HACD4, and TP53BP1, what is the significance of finding frameshift mutations in genes such as MFN1, LCMT2, RNMT, TRMT6, METTL8, and METTL16 in colorectal cancer?

The discovery of frameshift mutations in genes such as MFN1, LCMT2, RNMT, TRMT6, METTL8, and METTL16, in addition to ANK3, HACD4, and TP53BP1, broadens the understanding of the genetic landscape of colorectal cancer. MFN1, a mitochondrial membrane protein and tumor suppressor, and the other genes all contribute to a variety of cellular functions. Their mutations suggest that multiple cellular pathways are disrupted in colorectal cancer, contributing to its development and progression. Identifying these mutations helps paint a more complete picture of the genetic factors driving the disease and provides additional potential targets for therapeutic intervention. Future research may focus on how these mutations interact and influence cancer behavior, potentially leading to more comprehensive treatment strategies. Understanding the individual and combined roles of these genes is vital for creating personalized therapies that can effectively target the diverse genetic profiles found in colorectal tumors.