L14 - Soft tissue tumours: how rare entities are now a pilot for the medicine of tomorrow (Dr Francesca Maggiani) Flashcards
- Introducing the concept of soft tissue tumours as by the most recent WHO classification - Describing the morphology and genetics of some of the most common/characteristic soft tissue tumours - Explaining the implication that the morphological genetic classification has for the treatment
What are sarcomas?
Sarcomas are rare tumors that arise from mesenchymal tissues, such as fat, muscle, nerves, and blood vessels.
How do sarcomas differ from epithelial and haematological malignancies
Unlike epithelial malignancies (carcinomas, adenocarcinomas) and haematological malignancies (leukaemia’s, lymphomas), sarcomas are derived from connective and structural tissues rather than epithelial or blood-forming cells.
Where can mesenchymal tumours be found in the body?
🏥 Mesenchymal tumors can be found in two main locations:
- Associated with organs – Example: Leiomyoma of the uterus (benign smooth muscle tumor) and Leiomyosarcoma (malignant form).
- In soft tissue – Found in nerves, blood vessels, adipose (fat) tissue, fibrous tissue, skeletal muscle, and smooth muscle.
Why are mesenchymal tumours often handled by tertiary referral centres?
🏛️ Because mesenchymal tumors are rare, they require specialized expertise for diagnosis and treatment. Tertiary referral centers focus on these specific tumors, making it easier to conduct research, specialized training, and controlled studies on their diagnosis and treatment.
What is the role of genetics in the diagnosis and treatment of mesenchymal tumours
🧬 Advances in genetics have significantly changed how mesenchymal tumors are diagnosed and treated. Initially, tumors were identified based on morphology (appearance under a microscope), but now, genetic profiling helps classify tumors more accurately, leading to better-targeted treatments.
What are the primary types of soft tissue that can develop mesenchymal tumours?
💡 Soft tissue of mesenchymal origin includes:
1️⃣ Adipose tissue (fat)
2️⃣ Skeletal muscle
3️⃣ Nerves
4️⃣ Blood vessels
5️⃣ Fibrous tissue
⚠️ Note: Soft tissue is also present within organs and skin, so mesenchymal tumors can develop in these areas as well.
What are the different categories of soft tissue tumours in the WHO classification?
📚 The WHO classification of soft tissue tumors includes:
1️⃣ Adipocytic tumors (related to fat cells)
2️⃣ Fibroblastic and myofibroblastic tumors (derived from fibroblasts or myofibroblasts)
3️⃣ Fibrohistiocytic tumors (containing both fibroblast and immune-like cells)
4️⃣ Vascular tumors (originating from blood vessel cells)
5️⃣ Pericytic tumors (arising from pericytes, which surround blood vessels)
6️⃣ Smooth muscle tumors (from smooth muscle tissue, such as in blood vessels)
7️⃣ Skeletal muscle tumors (from voluntary muscle tissue)
8️⃣ Chondro-osseous tumors (forming bone or cartilage)
9️⃣ Peripheral nerve sheath tumors (from nerves)
🔟 Tumors of uncertain differentiation (poorly classified due to ambiguous features)
How are soft tissue tumours identified and diagnosed?
🔬 Diagnosis follows a multi-step approach:
1️⃣ Morphology – Examining tumor appearance under a microscope.
2️⃣ Immunohistochemistry – Using specific markers to confirm tissue origin.
3️⃣ Genetics – In some cases, genetic testing is necessary for classification.
⚠️ If morphology and immunohistochemistry give ambiguous results, the tumor may be classified under tumors of uncertain differentiation.
Where are superficial soft tissue tumours commonly found?
🏥 Superficial soft tissue tumors are usually located in the dermis or subcutaneous fat.
what are key characteristics for superficial soft tissue tumours?
✅ 99% are superficial
✅ 95% are smaller than 5 cm
✅ Often found in the skin, chest wall, trunk, retroperitoneum, and limbs
✅ Can be challenging to diagnose due to overlapping features with melanocytic and epithelial tumors
How do tumour types relate to location, age and symptoms?
🎯 While not absolute, there are patterns in tumour presentation:
✔️ Certain tumours are age-specific (e.g., common in children, young adults, or older adults)
✔️ Some tumours affect a wide age range (22–95 years)
✔️ Tumours can be linked to specific locations in the body (e.g., head & neck, limbs, gastrointestinal tract, retroperitoneum)
✔️ Some tumours are associated with germline mutations (syndromic conditions), while others have no known genetic link
What is the age distribution for sarcomas, and where are they commonly found?
📊 Sarcomas most commonly occur in the sixth and seventh decades of life (50s–70s).
📍 Common locations:
1️⃣ Chest wall, trunk, retroperitoneum (largest group)
2️⃣ Limbs
3️⃣ Head and neck
4️⃣ Gastrointestinal tract
5️⃣ Skin (difficult to diagnose due to similarities with melanocytic and epithelial tumors)
What is the most common type of soft tissue sarcoma?
🧬 Liposarcoma is one of the most common types of soft tissue sarcomas. However, the classification is continuously evolving, allowing for more precise subtyping of rare soft tissue tumors.
What makes rare soft tissue tumours difficult to diagnose?
🔍 Rare soft tissue tumours may have specific genetic mutations that define them. If a key mutation is not found, diagnosis can be challenging. Some tumours remain unclassified due to their infrequency and incomplete genetic profiling.
What is the key genetic feature of soft tissue tumours?
🧬 Chromosomal translocations are a hallmark of soft tissue tumours. These translocations fuse two genes together, triggering tumour growth. This differs from carcinomas, which typically have mutations activating cell proliferation pathways.
What are the key genetic differences between carcinomas and sarcomas?
🧬 Carcinomas usually have point mutations activating specific pathways, while sarcomas are often caused by chromosomal translocations, where two genes fuse to create an abnormal protein that drives tumor growth.
What is an example of a translocation associated with sarcomas?
🔗 The EWSR1 gene is commonly involved in sarcomas. A key example is EWSR1-FLI1 (t[11;22]), which is diagnostic for Ewing sarcoma, a small, undifferentiated tumour seen in children and young adults.
Why do different sarcomas sometimes share the same translocation
🔄 Some sarcomas with different morphology and behaviour can have the same translocation but with different fusion partners. This suggests that additional genetic factors influence tumor characteristics beyond just the translocation itself.
What are other common genes involved in sarcoma translocations?
🧬 Besides EWSR1, other frequently involved genes include:
✔️ FUS
✔️ WT1
✔️ ERG
How does tumor classification improve with modern research?
🏷️ New classifications allow for more precise identification of tumor subtypes. As genetic testing improves, we can distinguish rare tumors by their unique mutations and abnormal translocations making diagnosis and treatment more accurate
How do carcinomas and sarcomas differ in their genetic changes?
🔬 Carcinomas often have mutations that activate cell proliferation pathways, while sarcomas are typically driven by chromosomal translocations, which fuse two genes together and lead to tumor formation.
What makes Ewing sarcoma unique in terms of histology and genetics?
🏥 Ewing sarcoma is a small, round, undifferentiated tumor that resembles embryonic cells. It is characterized by the EWSR1-FLI1 translocation (t[11;22]), which is diagnostic for this tumor.
Why do some sarcomas with different behaviors share the same genetic translocation?
🔄 The same translocation can occur in different tumors, but their behavior and morphology vary. This suggests that additional genetic or environmental factors contribute to the specific tumor type and its aggressiveness.
Why are sarcomas challenging to diagnose clinically?
🏥 Sarcomas are often rare, highly variable, and can mimic other tumor types (e.g., epithelial or melanocytic tumors). They may also alter surrounding tissue, making clinical and histological diagnosis difficult.
What factors influence where a sarcoma develops in the body?
📍 Sarcomas can arise anywhere, but their location is influenced by:
✔️ Age (e.g., Ewing sarcoma in younger patients)
✔️ Tissue type (e.g., liposarcoma in fatty tissue)
✔️ Genetic mutations (e.g., EWSR1 in soft tissue and bone)
What are the challenges of diagnosing sarcomas in the skin?
⚠️ In the skin, mesenchymal tumors must be distinguished from:
✔️ Melanocytic tumors (e.g., melanoma)
✔️ Epithelial tumors (e.g., carcinoma)
✔️ Soft tissue tumors affecting the dermis
Overlapping features can make diagnosis complex and require genetic testing.
what are lipoma
🟡 Lipoma is the most common benign mesenchymal tumor, composed of mature adipose (fat) tissue.
How do lipomas typically apear
It typically appears as a soft, mobile lump under the skin, enclosed in a thin, shiny capsule.
How do lipomas appear under the microscope?
🔬 Lipomas contain large, empty-appearing fat cells (adipocytes) with small, peripheral nuclei. They show no mitotic activity, minimal atypia, and are well-circumscribed.
What are the clinical features of lipomas?
🏥 Lipomas are usually:
✔️ Soft, painless lumps under the skin
✔️ Well-circumscribed with a thin capsule
✔️ Yellowish in appearance due to fat content
✔️ Found in subcutaneous fat, often on the trunk, neck, or limbs
What is a spindle cell lipoma?
🔍 A spindle cell lipoma is a benign fat tumour seen mostly in elderly men, often in the neck or shoulder. It has spindle-shaped cells and mild atypia but remains non-cancerous.
What is the immunohistochemistry marker for a spindle cell lipoma
✔️ CD34+ immunohistochemistry marker
What is an angiolipoma, and why is it painful?
❤️ Angiolipoma is a benign fat tumor with numerous blood vessels, often found in the wrists or arms. It can be painful due to thrombi (blood clots) forming in its blood vessels. Ut is common in young adults
What is a hibernoma, and where does it occur?
🟤 Hibernoma is a benign fat tumor made of brown fat, a type of fat typically found in embryos. It occurs in unusual locations like the back (near the scapula) or deeper tissues.
What is hibernoma associated with?
✔️ Associated with UCP1 expression (a marker of brown fat)
How do lipomas differ from malignant fat tumors?
⚠️ Unlike liposarcomas, lipomas are:
✔️ Well-circumscribed
✔️ Uniform in fat cell size
✔️ Lacking mitotic activity
✔️ Not infiltrative into surrounding tissues
What are the key differences between a lipoma and a liposarcoma?
Lipoma (Benign) vs. ⚠️ Liposarcoma (Malignant):
- Growth: Lipomas grow slowly, while liposarcomas can grow rapidly.
- Capsule: Lipomas have a well-defined, thin capsule; liposarcomas are poorly circumscribed and may infiltrate surrounding tissue.
- Fat Cells: Lipomas contain uniform, mature fat cells; liposarcomas have atypical lipoblasts with nuclear atypia.
- Mitotic Activity: Lipomas have little to no mitotic activity, while liposarcomas show increased mitotic activity.
- Necrosis: Rare in lipomas but can be present in aggressive liposarcomas.
- Symptoms: Lipomas are usually painless; liposarcomas may cause pain or compress nearby structures.
- Location: Lipomas are typically superficial (subcutaneous fat), whereas liposarcomas are often deep-seated in soft tissues.
What is a Well-Differentiated Liposarcoma (Atypical Lipomatous Tumour)?
✅ A well-differentiated liposarcoma is a low-grade malignant tumour that arises from fat cells. It is the most common malignant adipocytic tumour, accounting for 40-45% of all liposarcomas.
Who is affected by Liposarcomas
👥This tumour primarily occurs in adults between the ages of 40 and 60 and is very rare in children.
Where do liposarcomas occur
It is commonly found in the retroperitoneum, limbs, and other soft tissues.
What are the genetic characteristics of liposarcomas
It is characterized by amplification of the MDM2 gene, which plays a role in tumour development.
How does a Well-Differentiated Liposarcoma behave?
Although it is technically malignant, a well-differentiated liposarcoma does not metastasize in most cases. However, it can be locally aggressive, meaning it may grow and invade nearby tissues
what is the risk of recurrence in liposarcomas?
🔄 The risk of recurrence is high, particularly when the tumour is located in the retroperitoneum, where complete surgical removal is often difficult.
What do liposarcomas look like under the microscope
🔬 This tumour consists of large fat cells with scattered atypical cells (lipoblasts), which have enlarged, irregular nuclei.
How are liposarcomas treated?
💊 The main treatment is wide surgical excision, and in some cases, radiation therapy may be used to reduce the risk of recurrence.
What is a dedifferentiated liposarcoma?
⚠️ A dedifferentiated liposarcoma is a more aggressive form of liposarcoma that arises from a previously well-differentiated liposarcoma.
How often does dedifferentiation occur?
🔄 This transformation occurs in about 10% of cases, especially in tumours located in the retroperitoneum.
In what age group is dedifferentiation of liposarcomas most common?
👴 more common in older adults, with a slight preference for men.
what is a genetic feature of a dedifferentiated liposarcoma
🧬 Like well-differentiated liposarcoma, it involves MDM2 gene amplification, but additional genetic mutations contribute to its more aggressive behaviour.
How does a dedifferentiated liposarcoma behave?
📈 A dedifferentiated liposarcoma grows more rapidly than a well-differentiated liposarcoma and has a higher risk of recurrence and metastasis.
How does a dedifferentiated liposarcoma appear under the microscope
🧬 There is often a sharp transition from well-differentiated fat cells to high-grade, poorly differentiated tumour cells, which look very abnormal and aggressive.
How are dedifferentiated liposarcomas treated?
🩺 Treatment involves surgical removal, but due to its aggressive nature, chemotherapy and radiation therapy are often required.
Why is a retroperitoneal liposarcoma more dangerous?
📏 When a liposarcoma occurs in the retroperitoneum (the space at the back of the abdomen), it has room to grow without being detected early.
Which organs may be displaced by retroperitoneal liposarcoma?
🩻 By the time it is diagnosed, the tumour is often very large and may displace organs such as the stomach, intestines, and kidneys.
Why is surgical removal or retroperitoneal liposarcoma more challenging and risky?
🩸 The tumour is located near major blood vessels like the aorta and vena cava, making surgical removal much more challenging and risky.
⚠️ Even if it is initially well-differentiated, incomplete removal increases the risk of recurrence, and each recurrence increases the chance of it becoming a dedifferentiated liposarcoma, which can metastasize.
Why is the same tumour (as a retroperitoneum) called an “Atypical lipomatous tumour” in soft tissue?
🦵 When this tumour occurs in the limbs or other soft tissue rather than the retroperitoneum, it is easier to detect and completely remove with surgery. Because of this it can be filly excised with good margins so has a lower risk of recurrence and does not usually metastasise.
🏥 In some countries, especially the United States, calling it an “Atypical Lipomatous Tumour” instead of “Well-Differentiated Liposarcoma” is done to avoid classifying the patient as having cancer, which could increase insurance costs. However, both terms describe the same tumour with the same genetics and morphology.
What is Myxoid Liposarcoma?
✅ Myxoid Liposarcoma is a type of high-grade soft tissue sarcoma that arises from fat cells but has very few mature fat cells compared to other liposarcomas. Instead, it contains tiny primitive cells in a myxoid (gel-like) background.
who is affected by Myxoid liposarcoma?
👥 It is more common in young adults, typically peaking in the 4th and 5th decades of life. Unlike many other sarcomas, there is no gender preference.
Where does myxoid liposarcoma occur?
It most commonly affects the extremities, particularly the proximal thigh.
Is Myxoid liposarcoma found in the retroperitoneum?
🚫 A primary retroperitoneal myxoid liposarcoma is extremely rare, but metastases to the retroperitoneum are more common.
How does Myxoid Liposarcoma appear under the mucroscope?
🔬 This tumour is unique because it does not have the typical yellowish fat-rich appearance of most liposarcomas. Instead, it has:
🩸 Numerous blood vessels, arranged in a highly characteristic branching pattern.
🦠 Small, primitive tumour cells with minimal cytoplasm.
🫧 A myxoid (gel-like) background, giving the tumour its name.
🔄 Some signet ring lipoblasts, which are cells with a nucleus pushed to the side by fat droplets.
What genetic abnormalities are found in Myxoid Liposarcoma?
🧬 Unlike other liposarcomas that involve MDM2 amplification, myxoid liposarcomas have specific gene fusions:
🔗 Most common: t(12;16)(q13;p11.2) → FUS-DDIT3 fusion
🧬 Rare (~2%) cases: t(12;22)(q13;q12) → EWSR1-DDIT3 fusion
How can the genetic abnormalities in Myxoid Liposarcoma be detected?
🧪 translocations can be detected using fluorescence in situ hybridization (FISH) or more advanced genetic testing like next-generation sequencing (NGS).
How does Myxoid Liposarcoma respond to treatment?
💡 One major advantage of myxoid liposarcoma is that it responds very well to radiotherapy. –> When treated with radiation, the tumour shrinks significantly, making surgical removal easier and less aggressive
What can radiation induce to myxoid liposarcoma?
🧪 Radiation can also induce changes in the tumour, leading to:
✅ More mature fat cells (adipocytic differentiation)
✅ Fibrosis (scarring), which makes excision easier
does myxoid liposarcoma metastasise?
⚠️ Yes, it is a high-grade tumour, so it has a risk of metastasis e.g. to the lung, bone and retroperitoneal. To make sure metastases doesn’t occur, regular follow-ups are required.
What improves myxoid liposarcoma outcomes?
👨⚕️ Early detection and treatment improve outcomes, especially when radiotherapy and surgery are combined.
Where do smooth muscle tumours originate from?
Smooth muscle tumours can arise from:
🩸 Blood vessels – Often linked to vessel walls in deep and superficial tissues.
💇 Piloerector muscles – Found in the skin, responsible for goosebumps.
Where do smooth myscle tumours typically occur in the body?
🩸 Blood vessels – Many smooth muscle tumours in superficial and deep soft tissues are linked to blood vessels.
💇 Skin (dermis) – They can arise from piloerector muscles, which are responsible for goosebumps.
🫁 Organs – These tumours can also form in the walls of internal organs, such as the uterus, intestines, or lungs.
How do smooth muscle tumours appear?
They can have different growth patterns:
🟠 Well-circumscribed lumps – These are rounded and easy to distinguish from surrounding tissue.
🩸 Vessel-associated tumours – These grow around blood vessels.
⚠️ Infiltrative tumours – These spread into nearby tissues, making them harder to remove completely.
Are there any risk factors for developing smooth muscle tumours?
⚠️ Some smooth muscle tumours have been linked to:
🦠 Epstein-Barr virus (EBV) infection
🦠 Immunosuppression, such as in organ transplant patients or those with HIV/AIDS
🧬 Genetic mutations, though less frequently
What are the key features of cutaneous smooth muscle tumours?
🩹 Superficial – Found just under the skin.
🔵 Small & multiple – Often appear in clusters.
⚡ Painful – Can cause discomfort, unlike many other benign tumour
Where do leiomyosarcomas typically arise from?
Leiomyosarcomas arise from smooth muscle cells, most commonly in the blood vessels or soft tissues
Where are Leiomyosarcomas frequently found?
They are frequently found in the extremities (arms and legs), the retroperitoneum (the area behind the abdominal organs), and sometimes in organs like the uterus. In rare cases, they can also occur in the bone, breast, colon, epididymis, or mediastinum (chest area).
How can you tell a leiomyosarcoma apart from a benign smooth muscle tumour?
✅ A leiomyoma is a benign smooth muscle tumour that is well-circumscribed, grows slowly, and does not invade surrounding tissues. It has few mitotic figures (dividing cells) and lacks necrosis (cell death).
❌ A leiomyosarcoma, on the other hand, is malignant and shows higher mitotic activity, larger and irregular nuclei (atypia), and areas of necrosis. Unlike leiomyomas, they can spread to other tissues and often require aggressive treatment.
What are the key microscopic features of a leiomyosarcoma?
🔬 Under the microscope, leiomyosarcomas have spindle-shaped cells with elongated nuclei and abundant eosinophilic (pink) cytoplasm. Atypia is present, meaning the nuclei look irregular and enlarged. The tumour also has increased mitotic figures, showing rapid cell division. If necrosis is present, it suggests a higher-grade tumour with more aggressive behaviour.
What is the significance of tumour location in leiomyosarcoma?
📍 The location of an LMS plays a significant role in its behaviour and treatment options. Tumours in the retroperitoneum are particularly challenging because they have room to grow undetected before causing symptoms. They may also be difficult to remove completely due to their proximity to major blood vessels and organs. However, LMS in the limbs or superficial soft tissues is often detected earlier and can be excised with wider margins, improving the chances of complete removal.
Why are some smooth muscle tumours classified as “uncertain malignant potential” (UMP)?
🤔 Some tumours do not clearly fit into either the benign or malignant category. These tumours might have some atypia (abnormal nuclei) but no necrosis, or they might show increased mitotic activity but otherwise look bland. Since it is difficult to predict their behaviour, they are classified as tumours of uncertain malignant potential (UMP). Patients with these tumours usually require careful monitoring to check for recurrence or aggressive behaviour over time.
what are the malignant mitotic rates at different sites?
The number of mitotic figures (dividing cells) per 10 high-power fields (HPF) is crucial.
- Soft tissue LMS: More than 1-2 mitoses/10 HPF.
- Skin/subcutaneous LMS: More than 2 mitoses/10 HPF.
- Retroperitoneal LMS: More than 5 mitoses/10 HPF, or 1-4 mitoses/10 HPF if necrosis is present and the tumour is larger than 7.5 cm.
What is a rhabdomyoma?
A rhabdomyoma is a rare benign tumour of mature skeletal muscle.
What are the different types of Rhabdomyoma?
👶 Fetal type – Occurs in infants and young children.
👩🦰 Adult type – Most common in men around 60 years old.
🖕Genital type – Found in the vulva, vagina, and other genital areas.
Where are Rhabdomyomas (Skeletal muscle tumours) commonly found in the body?
👩🦰Head and neck region, especially the oral cavity.
Less commonly found in other areas of the body.
What are the key features of Rhabdomyoma
- Not associated with tuberous sclerosis.
- Some cases may arise due to muscle degeneration and regeneration.
- Very rare, with a male predominance (75%).
What age group is affected by Rhabdomyosarcoma?
- Young children (~4-5 years old).
- Teenagers and young adults.
- Elderly patients (rarely).
What are common locations for Rhabdomyosarcoma
- Head and neck (including orbit and perimeningeal areas).
- Genitourinary tract (e.g., vagina, perianal region).
- Extremities (arms and legs).
What are the subtypes of rhabdomyosarcoma
1️⃣ Embryonal RMS (most common) – Often linked to TP53 mutations and p53 overexpression.
Botryoid variant – Occurs in very young children.
2️⃣ Alveolar RMS – More aggressive, often seen in older children and teenagers.
3️⃣ Pleomorphic RMS – Mainly affects adults and has a poor prognosis.
What are diognostic features of rhabdomyosarcoma
🔬 Shows myogenic differentiation (positive for MyoD1 and myogenin).
🔬 Unlike some other sarcomas, no specific gene fusion is associated.
🔬 Often displays recurrent copy number changes in the genome.
What is prognosis and treatment like for rhabdomyosarcom
- Anaplasia (abnormal cell structure) is linked to worse outcomes.
- Requires aggressive treatment with surgery, chemotherapy, and/or radiation.
What is botryoid embryonal rhabdomyosarcoma?
Botryoid embryonal rhabdomyosarcoma is a subtype of rhabdomyosarcoma that arises in mucosal-lined hollow organs.
What are common locations for botryoid embryonal rhabdomyosarcoma?
📍Bladder
📍Biliary tract & extrahepatic bile ducts
📍Vagina
📍Upper respiratory tract (e.g., nasopharynx, sinuses)
📍Rarely found in the eyelid or anal region
What are microscopic features for botryoid embryonal rhabdomyosarcoma?
🔬 Composed of small, round blue cells.
🔬 Cells cluster near the surface of the mucosa and become less dense deeper down.
🔬 Shows some pinkish cytoplasm, indicating myogenic differentiation (expressing myogenin).
What is prognosis and treatment like for botryoid embryonal rhabdomyosarcoma?
Better prognosis compared to other rhabdomyosarcoma subtypes.
Responds well to chemotherapy.
Surgical excision is often necessary but can be highly invasive.
Are rhabdomyosarcomas linked to genetic syndromes?
✅ Most cases of rhabdomyosarcoma occur sporadically, but some can be linked to inherited syndromes.
what are genetic associations with rhabdomyosarcomas
🧬Most cases occur due to somatic mutations, with no inherited predisposition
🧬A small proportion arises in children with familial cancer syndromes, particularly those affecting the RAS or Hedgehog pathways
What are some syndromes linked to rhabdomyosarcoma?
🧑⚕️ Costello syndrome (HRAS mutation)
🧑⚕️ Neurofibromatosis type 1 (NF1) – more commonly linked to neurogenic tumors
🧑⚕️ Noonan syndrome (PTPN11 & others)
🧑⚕️ Beckwith-Wiedemann syndrome (Chromosome 11p15 changes)
🧑⚕️ Dicer syndrome (DICER1 mutations)
🧑⚕️ Li-Fraumeni syndrome (TP53 mutations)
🧑⚕️ Gorlin syndrome (PTCH1 mutations)
What is the 1000 genome project (2008-2015) ?
✅ Aimed to identify and characterize genetic variations in human genomes
✅ Sequenced 2600 individuals from 26 global populations
✅ Used low-coverage whole-genome sequencing, SNP arrays, and deep exome sequencing
✅ Helped uncover common genetic polymorphisms (≥1% frequency) across populations
✅ First large-scale genome sequencing project, creating a freely available database for research
What is the 100,000 genomes project (UK, 2013 - 2018)
✅ Expanded genome sequencing to 100,000 whole genomes
✅ Focused on rare diseases and cancer genetics
✅ Integrated genomic data into the NHS, enabling personalized medicine
✅ Led to the first clinical diagnoses based on whole-genome sequencing
✅ Showed how genetic insights can guide treatment strategies
Why are the 1000 and 100,000 genome projects important for sarcoma research?
📌 Sarcomas are rare, making it hard to study them in large numbers
📌Genomic data helps identify mutations that drive different sarcoma subtypes
📌Aids in targeted therapy, ensuring the best possible treatment for each patient
What is Whole Genome Sequencing (WGS)?
🧬 Whole genome sequencing (WGS) is a technique used to determine the complete DNA sequence of an organism. It helps identify mutations that may contribute to diseases like cancer and genetic disorders.
Why is WGS important for medical research?
🔎 WGS is a powerful tool in medical research because it helps detect genetic variations, including:
1️⃣ Single nucleotide polymorphisms (SNPs) – Small DNA changes.
2️⃣ Copy number variations (CNVs) – Changes in the number of gene copies.
3️⃣ Structural variants – Large-scale DNA alterations.
How does WGS help in cancer diagnosis?
🏥 WGS allows doctors to analyze tumor DNA, identifying specific genetic abnormalities. This can help:
Confirm or change a diagnosis.
Identify targeted therapies.
Predict how a tumor will behave.
What makes fresh tissue analysis challenging?
🧪 Unlike traditional biopsies (which are preserved in formalin), fresh tissue samples must be processed immediately. This requires quick coordination between doctors, lab teams, and equipment.
How has WGS changed the way biopsies are handled?
📦 Traditionally, biopsy samples were preserved in formalin and processed later. Now, with WGS, some tissue is immediately frozen and analyzed.
🚨 This requires rapid coordination between medical teams but leads to faster, more accurate diagnoses.
What happens if a biopsy has limited tissue?
Sometimes, a biopsy does not contain enough high-quality DNA for sequencing. In these cases, doctors may:
🩺 Use alternative sequencing methods (like targeted panels).
🩺Rely on liquid biopsies to analyze tumor DNA from the blood.
can WGS help in rare cancers?
🎯 Yes! Rare cancers, like alveolar rhabdomyosarcoma, have few cases, making research difficult. However, if WGS finds mutations that are also present in other cancers, existing treatments could be repurposed.
❓ What is Next-Generation Sequencing (NGS)?
🚀 Next-Generation Sequencing (NGS) is an advanced technique that allows doctors to:
- Analyze DNA and RNA more efficiently.
- Detect translocations (which help diagnose tumors).
- Identify additional mutations that could influence treatment.
How can WSG improve early cancer detection
🩸 Some hospitals now use circulating tumor DNA (ctDNA) in blood to detect cancer earlier than traditional scans or biopsies. This liquid biopsy method is:
✅ Less invasive
✅ Faster
✅ More convenient for patients
How does liquid biopsy compare to traditional scans?
📊 Traditional imaging (like CT scans) may miss tiny tumors.
🩸 Liquid biopsies can detect tumor DNA earlier, improving monitoring and treatment decisions
How is WGS used beyond cancer research?
❓ How is WGS used beyond cancer research?
🌍 Genomics is transforming many areas of medicine, including:
👶 Newborn screening – Identifying rare diseases early.
🤰 Prenatal testing – Detecting fetal DNA in maternal blood for early diagnosis.
🧬 Rare disease research – Finding genetic causes of inherited conditions.
How is WGS used in hospitals today?
🏥 Many hospitals now routinely sequence tumors to:
Identify genetic mutations that guide treatment.
Detect recurrence risks early.
Improve diagnostic accuracy.
What is personalised medicine?
🎯 Personalized medicine tailors treatments based on a patient’s unique genetic profile.
🛠 Instead of a “one-size-fits-all” approach, doctors can:
✅ Match treatments to specific mutations.
✅ Avoid ineffective therapies.
✅ Improve patient outcomes.
How does WGS help find a new drug target?
💊 If WGS identifies genetic mutations in a rare cancer that also appear in a common cancer, existing drugs may be repurposed.
🔬 This speeds up treatment development and reduces costs.
How does WGS improve rare cancer treatments?
🔗 By identifying genetic links between rare and common cancers, WGS helps:
Find shared drug targets.
Improve early detection.
Develop personalized therapies.
What other medical areas use WGS?
🔬 WGS is used for more than just cancer! It helps in:
👶 Newborn screening – Identifying genetic conditions early.
🧬 Rare disease diagnosis – Finding inherited disorders.
🤰 Prenatal testing – Detecting fetal DNA for non-invasive genetic screening.
💊 Pharmacogenomics – Predicting how patients respond to medications.
