This document discusses common malignancies in children and embryonal tumors specifically. It outlines four main embryonal tumors - Wilms tumor, retinoblastoma, neuroblastoma, and medulloblastoma. For each tumor, it describes the clinical presentation, cellular origins based on embryonic development, molecular pathology including key genetic drivers, and current treatment approaches. It concludes by noting certain genetic predisposition syndromes can increase the risk of developing cancer in childhood.
Improving children and their families experience of the cancer care pathwayUCLPartners
Presentation by Zoe Berger, Joint Chair of the London Cancer Patient Experience Sub Group, at the Teenager and Young Adults Study Day, held on 25 July 2013.
A summer camp for children with serious medical conditions, The Painted Turtle was co-founded in 1999 by Paul Newman and Page and Lou Adler. Through the support of volunteers, campers engage in activities designed to build confidence, enhance friendships, and foster personal and community growth.
Presenter: Fares Kayali, Senior Researcher Vienna University of Technology. University of Applied Arts Vienna, AT
Event: Games for Health Europe 2015 Conference
Date: 03 NOV 2015 / 11:00 - 12:15
Location: Juliana Congreszaal, Jaarbeurs Utrecht
Presentation by Sara Portnoy of University College London Hospitals NHS Foundation Trust at the London Cancer Children, Teenager and Young Adults Study Day, held on 25 July 2013.
Nephroblastoma also known as Wilms tumor, is the most common renal malignancy affecting one in 10,000 children <15 years old
Children with bilateral disease are diagnosed at an earlier age (median age, girls at 31 months and boys at 24 months): Patients with associated congenital anomalies are also diagnosed at an earlier age
Accounts for 6-7% of cases of childhood cancer in the developed world and 12% in South Africa
In Tanzania the prevalence is 6.7% ( Mgaya E et al., 2000), “third from leukemia and lymphoma” (Shakilu J, 2017)
The overall survival rate of nephroblastoma approaches 90% in the developed world but in developing countries the survival rates are much less and in some sub-Saharan countries it is only 40% at 8 months after diagnosis
These may occur in 1% of infantile kidneys but typically regress during childhood
Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood: in contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100% of kidneys with bilateral disease
Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood: in contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100% of kidneys with bilateral disease
Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood: in contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100% of kidneys with bilateral disease
Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood: in contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100% of kidneys with bilateral disease
Has been associated with loss of function mutations of a number of tumor suppressor and transcription genes
These include mutations of the WT1, p53, FWT1, and FWT2 genes and at the 11p15.5 locus
Histologically, the classic favorable histology Wilms tumor is comprised of three cell types:
Blastemal cells – Undifferentiated cells
Stromal cells – Immature spindle cells and heterologous skeletal muscle, cartilage, osteoid or fat
Epithelial cells – Glomeruli and tubules
Grossly, Wilms tumors are usually well-circumscribed and have a pseudo-capsule
Histologically, Wilms is divided into "Favorable" and "Unfavorable" histologies
"Favorable" Histology: 90% of Wilms tumors will demonstrate "favorable" histology which generally has a better prognosis
Most children with Wilms tumor present with an abdominal mass or swelling without other signs or symptoms
The definitive diagnosis of Wilms tumor is made by histologic confirmation at the time of either surgical excision or biopsy
Stage I indicates the tumor was completely contained within the kidney without any breaks or spillage outside the renal capsule and no vascular invasion
Stage II would be a tumor that has grown outside the kidney
Stage IIIunresectable tumor
Stage IV-Metastasis
Stage V-bilateral kidney
Surgery is the main treatment
2021 World Cancer Day Campaign
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Neuroblastoma diagnosis, treatment, complications, and further management. The main contents of this review have been accessed from MedScape. Please do not reprint or copy this material without permission from the copyright owner.
Genetic and Epigenetic Basis of Paediatric AstrocytomasDenise Sheer
This is a presentation I gave to the Winter Meeting of the Pathological Society, 7th Jan 2016, in a symposium on Molecular Pathology for Risk Stratification. The symposium was organised together with the British Neuropathological Society.
This lecture was presented at the Steve Biko Academic Hospital in South Africa in Dec 2015. It describes the latest discoveries on molecular changes in children's gliomas, and shows how this information can be used for development of new types of treatment. It also includes an overview of the HeadSmart Campaign which aims to reduce the time to diagnosis for children with brain tumours.
Microhomology in Genomic Stuctural Variation - Diego Ottaviani, Magdalena Lec...Denise Sheer
THE ROLE OF MICROHOMOLOGY IN GENOMIC STRUCTURAL VARIATION, PUBLISHED IN TRENDS IN GENETICS, 2014.
OVERVIEW:Genomic structural variation, which can be defined as differences in the copy number, orientation, or location of relatively large DNA segments, is not only crucial in evolution, but also gives rise to genomic disorders. Whereas the major mechanisms that generate structural variation have been well characterised, insights into additional mechanisms are emerging from the identification of short regions of DNA sequence homology, also known as microhomology, at chromosomal breakpoints. In addition, functional studies are elucidating the characteristics of microhomology-mediated pathways, which are mutagenic. Here, we describe the features and mechanistic models of microhomology-mediated events, discuss their physiological and pathological significance, and highlight recent advances in this rapidly evolving field of research.
- Microhomology as a mutational signature
- Microhomology-mediated end joining (MMEJ)
- Replicative microhomology-mediated mechanisms
Fork stalling and template switching (FoSTeS)
Microhomology-mediated break-induced replication (MMBIR)
- Microhomology-mediated rearrangements in the germline
- Somatic microhomology-mediated rearrangements
Microhomology-mediated ligation in immune cells
Microhomology-mediated structural variation in cancer cells
FIGURES:
Figure 1. Microhomology at breakpoint junctions and flanking regions of simple gene fusions.
Figure 2. Nonhomologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ).
Figure 3. Double-strand break (DSB) repair pathway choice.
Figure 4. Mechanistic model of fork stalling and template switching.
Figure 5. Mechanistic model of microhomology-mediated break-induced replication (MMBIR).
Figure. S1. Microhomology at breakpoint junctions of microdeletions of the FOXL2 gene or its regulatory domain.
TABLES:
Table 1. Orthologous proteins reported to be involved in or inhibit MMEJ.
Table S1: Mechanisms that give rise to genomic structural variation.
Table S2. Examples of microhomology at rearrangement junctions.
"From the Chromosome...Everything". My Inaugural Lecture at the Blizard Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London. 10th May 2010.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
2. Overview
1. Outline the common malignancies in children
2. Describe the clinical presentation, cellular origins, molecular
pathology and treatment of the embryonal tumours:
a. Wilms tumour
b. Retinoblastoma
c. Neuroblastoma
d. Medulloblastoma
3. Describe the high-risk groups for developing cancer in childhood
3. 1. Outline the common malignancies in children
Background
• Childhood cancer is rare among childhood diseases
• Leading cause of death in children
• Distinct spectrum of malignancies at different ages
• Certain childhood cancers (“Embryonal”) reflect abnormal
processes of embryonic development
• No consistent environmental factors identified
• Can be predisposed by certain genetic disorders
• This lecture – Childhood Solid Tumours
5. National Registry of Childhood Tumours, Progress Report 2010
Improvements in Cancer Survival
6. Adapted from Robison & Hudson (2014)
Growth
&
Development
• Skeletal
matura+on
• Linear
growth
• Emo+onal
&
social
matura+on
• Intellectual
func+on
• Sexual
development
Psychosocial
• Mental
health
• Educa+on
• Employment
• Health
insurance
• Chronic
symptoms
• Physical/body
image
Cancer
• Recurrent
primary
cancer
• Subsequent
neoplasms
Fer8lity
and
reproduc8on
• Fer+lity
• Health
of
offspring
• Sexual
func+oning
Organ
func8on
• Cardiac
• Endocrine
• GI
&
hepa+c
• Genitourinary
• Musculoskeletal
• Neurological
• Pulmonary
Childhood
and
adolescent
cancer
Health and quality-of-life issues faced by cancer survivors
7. • Heterogeneous group of rare cancers
• Usually diagnosed in children before 5 years of age
• Originate in developing tissues and organ systems
• Examples
• Wilms’ tumour
• Retinoblastoma
• Neuroblastoma
• Medulloblastoma
• Hepatoblastoma
• Rhabdomyosarcoma
• Germ Cell Tumours
Embryonal tumours
This lecture
8. Possible explanations:
• Childhood tumours arise in cells that are naturally undergoing rapid developmental
growth, with fewer brakes on their proliferation than cells in adults.
• Tumour precursor cells are negotiating crucial developmental checkpoints that are
susceptible to corruption, leading to incomplete or abnormal cellular maturation
Low mutation frequency in children’s cancer
Strachan et al.
Genetics & Genomics
in Medicine (2015)
9. 2a. Wilms’ tumour
Clinical presentation
• Tumour of the kidney, also called Nephroblastoma
• Affects 1/10,000 children
• Most often in children under 5 years,
• Usually presents as asymptomatic abdominal mass without metastasis
• Spreads by growth, or via lymphatics or blood stream
• Heritable in ~5% of patients, often bilateral; can be associated with
predisposition syndromes, e.g.
- Wilms’ tumour, Aniridia, Genito-urinary abnormalities, mental Retardation
(WAGR)
- Beckwith-Wiedeman syndrome (BWS)
10. Wilms’ tumour
Cellular Origins
• Arises from pluripotent embryonic renal precursors
• Classically contains the three cell types present in the embryonic
kidney: blastema, epithelia, stroma
• Closely resembles developing nephrogenic mesenchyme
• Expresses markers of early kidney development
11. Rivera & Haber (2005)
Histological similarity between the developing kidney and Wilms’ Tumour
Embryonic kidney Wilms’ Tumour
B: Blastema
F: Mesenchyme
E: Epithelium
M: Condensing
mesenchyme
C: Comma-shaped
body
S: S-shaped body
G: Glomerulus
12. Wilms’ tumour
Molecular pathology
• Somatic activating mutations in CTNNB1; inactivating mutations in WT1,
WTX, TP53; epigenetic abnormalities at H19/IGF2 locus
• Congenital malformations associated with germline deletions or mutations
in the WT1 gene, including WAGR syndrome, in ~6% of cases
• Congenital malformations associated with germline deletions or mutations
in the H19/IGF2 locus, including BWS syndrome, in ~4% of cases
WT1 has a key role in ureteric branching; WT1 and the WNT pathway (which
is activated by β-catenin, CTNNB1) have key roles in epithelial induction of
the metanephric mesenchyme
Rivera & Haber (2005)
13. The WT1 gene in the developing kidney and Wilms’ Tumour
Scotting et al (2005)
14. Wilms’ tumour
Treatment
• Stage,
histology
and
age
at
diagnosis
are
prognos+c
factors
• Treatment
–
surgery
then
chemotherapy
(USA),
chemotherapy
then
surgery
(Europe)
• Use
of
radiotherapy
is
decreasing
• Combina+on
chemotherapy
shows
promising
results
• Counselling
is
essen+al
if
gene+c
predisposi+on
is
suspected
Gleason
et
al
(2014)
15. National Registry of Childhood Tumours, Progress Report 2012
Improvements in survival of Wilms’ tumour patients
16. Clinical presentation
• Tumour of the retina
• Usually occurs in children under 5 years, and accounts for ~5% of tumours in
this age group
• Appears to be more prevalent in sub-Saharan Africa than rest of world
• Heritable in ~30% of cases:
- positive family history
- bilateral or multifocal
- germline mutation of RB1 gene
- usually present at a younger age
• Symptoms include leukocoria (“white pupil” when light shone into it), eye pain
or redness, vision problems
• Metastatic disease in 10-15% of patients
2b. Retinoblastoma
18. Cellular origins
• Originates from cone precursor cells in which signalling pathways
suppress cell death and promote cell survival after loss of RB1
Retinoblastoma
Xu
et
al
(2014)
19. Molecular Pathology
• Whole genome sequencing shows very few genetic changes
• Loss of RB1 – key role in cell cycle regulation
• MYCN activation
• MDM2 or MDM4 amplification - leads to inactivation of p53 pathway
• SYK overexpression – required for tumour cell survival
Retinoblastoma
Zhang
et
al
(2012)
20. Treatment
• Treatment options consider both cure and preservation of sight
- Small tumours – cryotherapy, laser therapy or thermotherapy
- More advanced tumours or distant disease – chemotherapy, surgery &/or
radiation
- Systemic or intraocular chemotherapy can be used to shrink tumours before
cryotherapy or laser therapy
- Identification of SYK overexpression suggests targeted therapy approach
• Germline mutation of RB1 have increased risk of second cancer, especially if
receive radiation therapy
• Late effects include visual impairment and increased risk of secondary
malignancies, including bone and soft tissue sarcomas, and melanoma
Retinoblastoma
Abramson (2014)
21. National Registry of Childhood Tumours, Progress Report 2012
Improvements in survival of Retinoblastoma patients
22. Clinical presentation
• Tumour of the sympathetic nervous system, usually arising in the adrenal
gland or sympathetic ganglia
• Most common cancer in the first year of life
• Family history in 1-2% cases
• Metastatic disease in >50% cases at diagnosis; spreads via lymphatics
and blood stream
• Highly heterogeneous disease – extremes of risk
• Prognostic factors: stage, age, MYCN amplification, DNA ploidy,
histopathology
• Neuroblastoma 4S presents in infants, specific pattern of metastatic
disease to liver and skin, spontaneous maturation and regression without
cytotoxic therapy
2c. Neuroblastoma
Cheung & Dyer (2013)
23. Cellular origins
• Derived from the sympatho-adrenal lineage of the neural crest during
development
• The cell of origin is believed to be an incompletely committed precursor cell
The neural crest gives rise to diverse cell types including peripheral neurons,
enteric neurons and glia, melanocytes, Schwann cells, and cells of the
craniofacial skeleton and adrenal medulla
Neuroblastoma
24. Development of the sympatho-adrenal lineage of the neural crest
Cheung
&
Dyer
(2013)
26. Treatment
• Surgery, chemotherapy, radiation therapy
• High risk disease – high-dose chemotherapy and stem cell
transplantation
• Chemotherapy-related complications include hearing loss,
infertility, cardiac toxicity, & second malignancies
• Targeted therapy – crizotinib against ALK mutations
• Immunotherapy
Neuroblastoma
27. National Registry of Childhood Tumours, Progress Report 2012
Improvements in survival of Neuroblastoma patients
28. Clinical presentation
• Most common malignant brain tumour in children
• More prevalent in children under 10 years than older children
• Highly invasive embryonal tumour that arises in the cerebellum
• Early dissemination throughout the CNS
2d. Medulloblastoma
29. Molecular Pathology
• WHO Classification 2007 based on histology:
- Classic – intermediate risk
- Desmoplastic/Nodular – more favourable
- Large cell/Anaplastic – very poor outcome
• Molecular subtypes involving key developmental signalling pathways:
- WNT (Wingless) – most favourable
- SHH (Sonic hedgehog) – intermediate risk
- Group 3 – worst outcome
- Group 4 – intermediate risk
Medulloblastoma
Northcott et al (2012)
31. Cellular origins
• Genetic predisposition syndromes, gene expression profiling, and
mouse models have been crucial in identifying molecular and cellular
origins
• SHH subtype originates in cerebellar granule neuron precursor cells
via aberrant activation of the Sonic Hedgehog pathway
• WNT subtype originates in lower rhombic lip cells of the dorsal
brainstem via aberrant activation of β-catenin (CTNNB1)
• Group 3 appears to originate in cerebellar granule neuron precursor
cells &/or cerebellar neural stem cells via aberrant activation of MYC
• Origin of Group 4 is unknown
Medulloblastoma
Northcott et al (2012)
36. National Registry of Childhood Tumours, Progress Report 2012
Improvements in survival of Medulloblastoma patients
37. 3. High-risk groups for developing cancer in childhood
Genetic predisposition to childhood cancer
• Any tumour diagnosed in the perinatal period suggests a genetic
predisposition syndrome, also tumours with certain features in older children
• Bilateral or multifocal disease, associated with congenital malformations
• Cancer in close relatives
• Same rare tumour in more than one family member,
e.g. familial Retinoblastoma
• Different types of tumours occuring in family members,
e.g. Li-Fraumeni syndrome
• Genetic counselling is essential
38. Examples of genetic predisposition syndromes for childhood cancer
Syndrome
Gene/chromosome
Tumours
Developmental
defects
WAGR
11p13
dele+on
Wilms’
tumour
Aniridia,
genitourinary
abnormali+es,
mental
retarda+on
Beckwith-‐Wiedeman
11p15:
H19/IGF2
locus-‐
abnormal
imprin+ng
Hepatoblastoma,
adrenocor+cal
carcinoma,
Wilms’
tumour
Overgrowth
syndrome,
macroglossia,
omphalocele,
hemihypertrophy
Mul+ple
endocrine
neoplasia,
type
2B
RET
Medullary
thyroid
carcinoma,
Phaeochromocytoma
Mucosal
neuroma,
marfanoid
habitus
Basal-‐cell
nevus
PTCH1
Medulloblastoma;
basal-‐cell
carcinoma,
ovarian
fibromas
Macrocephaly,
hypertelorism,
palmar
or
plantar
pits,
rib
abnormali+es,
ectopic
calcifica+on
of
the
falx
cerebri
Li-‐Fraumeni
TP53
Brain
tumour,
bone
or
so]-‐
+ssue
sarcoma,
adenocor+cal
carcinoma;
breast
cancer,
leukaemia
-‐
Fam
Re+noblastoma
RB1
Re+noblastoma,
sarcoma,
melanoma;
glioma,
carcinoma
-‐
Fam
Neuroblastoma
ALK
Neuroblastoma
-‐
Medulloblastoma
SUFU
Medulloblastoma
-‐
39. D.H. Abramson (2014) Retinoblastoma: saving life with vision. Ann Rev Medicine 65:171-84
N-K.V. Cheung & M. Dyer (2013) Neuroblastoma: developmental biology, cancer genomics and immunotherapy.
Nat Rev Cancer 13:397-411
J.M. Gleason et al (2014) Innovations in the management of Wilms’ tumor. Ther Adv Urol. 6:165-176
T.J. MacDonald et al (2014) The rationale for targeted therapies in medulloblastoma. Neuro-Oncology 16:9-20
G.M. Marshall et al (2014) The prenatal origins of cancer. Nat Rev Cancer 14:277-289
P.A. Northcott et al (2012) Medulloblastomics: the end of the beginning. Nat Rev Canc 12:818-834
M.N. Rivera & D.A.Haber (2005) Wilms’ tumour: Connecting tumorigenesis and organ development in the kidney.
Nat Rev Cancer 5:699-712
L.L. Robison & M.M. Hudson (2012) Survivors of childhood and adolescent cancer: life-long risks and
responsibilities. Nat Rev Cancer 14:61-70
P.J.Scotting et al (2005) Childhood solid tumours: a developmental disorder. Nat Rev Canc 5:481-488
J. Zhang et al (2012) A novel retinoblastoma therapy from genomic and epigenetic analysis. Nature 481: 329-334
X.L. Xu et al (2014) Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature 514: 385-388
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