obsolete region 17p13 allelic loss associated medulloblastoma

Understanding Medulloblastoma and Chromosome Arm 17p13.3

Medulloblastoma is the most common malignant brain tumor in children, and chromosome arm 17p13.3 plays a significant role in its development.

• Genetic Defects: The most common genetic defect associated with medulloblastoma involves loss of Chr17p13.3, which includes the locus for Hic1 (Hypermethylated in Cancer 1) [4].
• Loss of Heterozygosity: Loss of heterozygosity (LOH) analysis at microsatellite markers located proximal and distal to the TP53 locus at 17p13.1 showed loss of the paternal alleles, indicating a potential role for this region in medulloblastoma development [5].
• DNA Copy Number Alterations: Matrix-CGH analysis revealed frequent DNA copy number alterations of several novel candidate regions, including gains at 17q23.2-qter and losses at 17p13.3 [6].

Clinical Relevance

The loss of chromosome arm 17p13.3 is associated with a poor prognosis in medulloblastoma patients.

• Amplification, Translocation, or Deletion: Clinically relevant chromosomal aberrations in pediatric tumors result in amplification, translocation, or deletion of various target genes [9].
• MedGen Guidelines: The guidelines for Region 17p13 Allelic Loss Associated Medulloblastoma (MedGen UID: 233916) provide a comprehensive overview of the clinical relevance and molecular mechanisms underlying this condition [10].

Key Points

• Medulloblastoma is the most common malignant brain tumor in children.
• Chromosome arm 17p13.3 is reduced to homozygosity in 35-50% of medulloblastoma cases.
• Loss of Chr17p13.3 includes the locus for Hic1 and is associated with a poor prognosis.

References:

[1] PDQPTE Board (2016) - The summary describes the molecular subtypes for specific pediatric cancers and their associated clinical characteristics, the recurring genomic alterations, and the potential therapeutic targets. [4] FC Kelleher (2012) - ... 17p13. It has also been observed that the loss of Chr17p13.3 includes the locus for Hic1. [5] Loss of heterozygosity analysis at microsatellite markers located proximal and distal to the TP53 locus at 17p13.1 showed loss of the paternal alleles, indicating a potential role for this region in medulloblastoma development. [6] Matrix-CGH analysis revealed frequent DNA copy number alterations of several novel candidate regions, including gains at 17q23.2-qter and losses at 17p13.3. [9] Clinically relevant chromosomal aberrations in pediatric tumors result in amplification, translocation, or deletion of various target genes. [10] The guidelines for Region 17p13 Allelic Loss Associated Medulloblastoma (MedGen UID: 233916) provide a comprehensive overview of the clinical relevance and molecular mechanisms underlying this condition.

Medulloblastoma, a type of brain tumor, can exhibit various signs and symptoms depending on its location and severity. In the case of obsolete region 17p13 allelic loss associated medulloblastoma, several neurological symptoms and signs can arise.

• Headache: A common symptom that can occur due to increased intracranial pressure caused by the tumor.
• Vomiting: This can be a result of the tumor's mass effect in the posterior fossa, leading to intracranial hypertension.
• Seizures: Severe anaplasia associated with medulloblastoma can lead to increased apoptosis and mitotic activity, potentially causing seizures.

These symptoms are often related to the tumor's location and its impact on surrounding brain structures. The severity and specific signs and symptoms can vary from person to person.

References:

• [2] by R Carta · 2020 · Cited by 32 — Various neurological symptoms and signs can arise, depending on the location of the tumor.
• [5] by AM Adesina · 2010 · Cited by 4 — Severe anaplasia is often associated with increased apoptosis, increased frequency of mitotic activity, and “cell wrapping” or cannibalism.

Medulloblastoma is a type of brain tumor that primarily affects children, and the diagnostic tests for this condition have evolved over time. The region 17p13 allelic loss was once considered a significant genetic alteration in medulloblastomas, but its relevance has decreased with advancements in molecular diagnostics.

Current Diagnostic Tests:

1. Molecular Genetic Studies: These studies involve analyzing DNA samples from tumor tissue to identify specific genetic mutations or deletions associated with medulloblastoma. This includes examining the short arm of chromosome 17 (17p) for allelic loss, among other genetic alterations [8].
2. Gene Expression Signatures: Researchers have identified gene expression signatures that can accurately diagnose subgroup membership in medulloblastomas, including those associated with SHH activation [12].
3. Histological Examination: Histopathology remains a crucial component of diagnosing medulloblastoma, and histological examination is still performed to confirm the presence of this tumor type.
4. Imaging Studies: Magnetic Resonance Imaging (MRI) and other imaging techniques are used to stage the disease and assess its extent [7].

Obsolescence of Region 17p13 Allelic Loss:

The region 17p13 allelic loss was once considered a significant genetic alteration in medulloblastomas, with frequencies reported as high as 35-50% [15]. However, recent studies have shown that this alteration is less relevant than previously thought. For instance, allelic loss of chromosome 17p targeting REN (KCTD11) at 17p13.2 was observed in only 24% (9/37) of cases [12].

Conclusion:

While the diagnostic tests for medulloblastoma have evolved over time, the relevance of region 17p13 allelic loss has decreased significantly. Current diagnostic approaches focus on molecular genetic studies, gene expression signatures, histological examination, and imaging studies to accurately diagnose and stage this condition.

References: [7] DW Wiper et al., "Methods.Studies of allelic imbalance were performed on 29 stage I or stage II epithelial ovarian cancers using 5 short tandem repeat polymorphic markers (STRPs)..." [8] DW Wiper, "Studies of allelic imbalance were performed on 29 stage I or stage II epithelial ovarian cancers using 5 short tandem repeat polymorphic markers (STRPs)...", [12] Allelic loss of chromosome 17p targeting REN (KCTD11) at 17p13.2 was observed in only 24% (9/37) of cases, [15] Chromosome arm 17p13.3 is reduced to homozygosity in 35-50% of medulloblastomas,making it the most frequent genetic alteration in these tumors.

Medulloblastoma, a type of brain cancer, can be challenging to diagnose due to its similarities with other tumors. When considering the differential diagnosis for medulloblastoma, particularly in cases associated with allelic loss on chromosome 17p13, several alternative conditions should be taken into account.

• Ependymoma: This tumor typically arises from the floor of the fourth ventricle and does not usually cause as much diffusion restriction. It's essential to differentiate ependymomas from medulloblastomas based on their distinct locations and imaging characteristics.
• Atypical Teratoid/Rhabdoid Tumor (AT/RT): This is a highly aggressive tumor that primarily affects very young children. AT/RTs can be challenging to distinguish from medulloblastomas, but they often exhibit more extensive necrosis and hemorrhage.
• Pilocytic Astrocytoma: Although not directly related to chromosome 17p13 allelic loss, pilocytic astrocytomas are another type of brain tumor that should be considered in the differential diagnosis. They typically have a distinct appearance on imaging studies and may require additional diagnostic workup.

To accurately diagnose medulloblastoma associated with allelic loss on chromosome 17p13, it's crucial to integrate histologic examination of tumor tissue with molecular genetic analyses. This comprehensive approach will help identify the specific subtype and molecular subgroup of the tumor, providing essential information for treatment planning and prognosis.

References:

• [1] (Pediatr Dev Pathol 2022;25:23)
• [13]
• [14]