Germline Mutations of Soft Tissue Sarcomas

Germline mutations of soft tissue sarcomas are sarcomas due to specific genetic factors. There are four main diseases in this category, and it is important to know these diseases so that patients can be diagnosed when they arrive at the hospital.

Neurofibromatosis Type 1

Neurofibromatosis Type 1 is an autosomal dominant inherited disease. It is caused by a mutation of the NF1 gene. The NF1 gene is located on chromosome 17, at 17q11.2. NF1 codes for a protein called neurofibromin, a tumor suppressor of the RAS Oncogene signaling pathway.

It is associated with the development of-

• Multiple cutaneous neurofibroma
• Malignant peripheral nerve sheath tumor – 10% risk of this development.
• Schwannomas
• Glioma 

Li-Fraumeni Syndrome

Li-Fraumeni Syndrome is an autosomal dominant syndrome. It is caused by the mutation of the TP53 gene. The TP53 is located on chromosome number 17, at 17p13.1

TP53 codes for protein P53, which acts as a tumor suppressor. Functions of wild type P53 are-

• It facilitates the clearance of damaged cellular DNA.
• It prevents the clonal propagation of these mutated sequences.

TP53 mutation results in an increased risk of malignancies. These malignancies are in decreasing order of frequency, are-

• Breast cancer
• Soft tissue sarcomas include rhabdomyosarcoma, undifferentiated pleomorphic, and pleomorphic sarcoma.
• Adrenocortical carcinoma
• Brain tumor
• Osteosarcoma
• Hematological Malignant Neoplasm

This means that a patient who is positive for the TP53 gene has the highest risk of developing breast cancer and the least risk of developing Hematological Malignant Tumours.

In these patients, annual body MRI, dedicated breast imaging, and colonoscopy are advised due to the risk of developing brain tumors, breast cancer, and colorectal cancer. Only if these investigations are done regularly can we expect to reduce the mortality risk related to these diseases. This a problematic diagnosis and the delay in diagnosis could mean a huge difference in life and death.

FAP (Familial Adenomatous Polyposis)

FAP is an autosomal dominant inheritance. FAP is caused by the mutation of the APC gene. The APC gene is located on chromosome 5 at 5q21. The APC gene codes for a protein that acts as a tumor suppressor. It inhibits the localization of beta-catenin to the nucleus. The cardinal feature of FAP is that there is development of multiple adenomatous polyps. Extra colonic manifestations of Familial Adenomatous Polyposis include-

• Epidermoid cysts.
• Osteomas.
• Desmoid tumor- arises five years after FAP-related prophylactic colectomy. It increases mortality and morbidity, mainly because desmoid tumor arises from prior surgical sites. 
• Usually, intra-abdominal desmoids are seen in FAP, and extremity desmoids are generally sporadic.

Gardner’s Syndrome

It is an autosomal dominant inheritance. It is a combination of FAP along with the following.

• Osteoma of mandible
• Benign lymphoid polyposis of ileum
• Congenital hypertrophy of the retinal pigment epithelium (CHRPE)
• Dental anomalies (patients have super-numerary teeth)
• Desmoids tumor
• Sebaceous cyst.

To read more about Soft tissue sarcomas, sign up for the SS Surgery program on the PrepLadder app. This topic and the other important topics have been taught in detail on the website. The related text can also be read from the notes section of the PrepLadder app. 

Also Read: Soft Tissue Sarcoma : Causes, Risk Factors

Frequently Asked Questions:

Q: What is the most common type of cancer in Li-Fraumeni syndrome (LFS)?

Answer: Breast Cancer

Q: What is the cause of Li-Fraumeni syndrome (LFS)

Answer:  It is caused by the mutation of the TP53 gene. 

Q: Where is the TP53 gene located on the chromosome?

Answer: The TP53 is located on chromosome number 17, at 17p13.1

Q: Malignant peripheral nerve sheath tumor is caused by the mutation of which gene?

Answer: NF1 gene

Q: Where is the NF1 gene located on the chromosome?

Answer: The NF1 gene is located on chromosome 17, at 17q11.2

Hope you found this blog helpful for your NEET SS Surgery Oncology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.