Compendium of Cancer Genome Aberrations

BRST5:Papillary ductal carcinoma in situ: Difference between revisions

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{{DISPLAYTITLE:Papillary ductal carcinoma in situ}}
{{DISPLAYTITLE:Papillary ductal carcinoma in situ}}
[[BRST5:Table_of_Contents|Breast Tumours (WHO Classification, 5th ed.)]]
[[BRST5:Table_of_Contents|Breast Tumours (WHO Classification, 5th ed.)]]
{{Under Construction}}
<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
==Primary Author(s)*==
==Primary Author(s)*==
Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith, PhD) </span>
Sresi Singh
==WHO Classification of Disease==
==WHO Classification of Disease==


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==Gene Rearrangements==
==Gene Rearrangements==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
No recurrent gene rearrangements have been identified in papillary DCIS, which is primarily characterized by mutations and copy number alterations.
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|-
|-
|
|
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|}
|}
==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
Copy-number alterations are common genomic events in ductal carcinoma in situ and other papillary breast neoplasms. Recurrent chromosomal changes include gains of chromosome arms 1q and 8q, loss of 16q, and amplification of 17q12 containing the ERBB2 gene, which contributes to HER2 overexpression in a subset of lesions.  
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|1
7
|Gain
|<span class="blue-text">EXAMPLE:</span> Loss
|1q
|<span class="blue-text">EXAMPLE:</span>
|
chr7
|P
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|Gain of chromosome 1q is frequently observed in early breast neoplasia including DCIS and contributes to tumor progression.
|<span class="blue-text">EXAMPLE:</span> D, P
|-
|<span class="blue-text">EXAMPLE:</span> No
|8
|<span class="blue-text">EXAMPLE:</span>
|Gain
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
|8q24
|MYC
|P
|No
|Gain of 8q results in MYC activation and increased cell proliferation in breast tumors.
|-
|11
|Gain
|11q13
|CCND1
|P
|No
|Amplification of CCND1 leads to dysregulated cell cycle progression and has been reported in breast tumors.
|-
|13
|Loss
|13q14
|RB1
|P
|No
|Loss of RB1 contributes to cell cycle dysregulation in breast cancer.
|-
|16
|Loss
|16q
|CDH1
|P
|No
|Loss of chromosome arm 16q is commonly associated with low-grade breast tumors and ductal carcinoma in situ.
|-
|17
|Amp
|17q12
|ERBB2
|D, P, T
|Yes (NCCN)
|Amplification of ERBB2 results in HER2 overexpression and may guide targeted therapy decisions in breast cancer.
|-
|-
|<span class="blue-text">EXAMPLE:</span>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|<span class="blue-text">EXAMPLE:</span>
|
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|
|
|
|
|-
|-
|
|
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|}
|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
Breast neoplasms including ductal carcinoma in situ frequently demonstrate chromosomal instability and aneuploidy, which contribute to copy-number alterations and genomic heterogeneity. In some tumors, defects in DNA repair pathways such as homologous recombination also contribute to mutational accumulation.  
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|Chromosomal instability (CIN)
Co-deletion of 1p and 18q
|Accumulation of chromosomal gains and losses due to defects in mitotic segregation and DNA repair pathways
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|Common (>20%)
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|P
|<span class="blue-text">EXAMPLE:</span> D, P
|No
|
|Chromosomal instability contributes to genomic heterogeneity and tumor evolution in breast tumors.
|
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|Aneuploidy
Microsatellite instability - hypermutated
|Abnormal chromosome numbers caused by chromosomal missegregation during cell division
|
|Common (>20%)
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|P
|<span class="blue-text">EXAMPLE:</span> P, T
|No
|
|Aneuploidy is frequently observed in breast tumors and is associated with tumor progression.
|
|-
|-
|
|Homologous recombination deficiency
|
|Homologous recombination deficiency
|
|Rare (<5%)
|
|P, T
|
|Yes
|
|HR deficiency may influence response to PARP inhibitor therapy in breast cancer; however, PARP inhibitor therapy is not applicable to in situ disease.
|}
|}
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
Breast tumors including ductal carcinoma in situ frequently harbor recurrent somatic mutations affecting pathways involved in cell proliferation, transcriptional regulation, and genomic stability. Commonly mutated genes include PIK3CA, TP53, and GATA3, among others. The mutational profile of papillary DCIS largely overlaps with other luminal-type breast neoplasms.  
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|PIK3CA
 
|Activating mutations
<br />
|Oncogene
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|Common
|<span class="blue-text">EXAMPLE:</span> Oncogene
|T
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> T
|Activates PI3K–AKT signaling pathway leading to increased cell growth and survival. Targeted therapy for invasive disease.
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|-
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|TP53
|Inactivating mutations
|TSG
|Recurrent
|P
|Yes
|Associated with genomic instability and aggressive tumor behavior
|-
|GATA3
|Inactivating mutations
|Other
|Recurrent
|P
|No
|Transcription factor regulating luminal cell differentiation in breast epithelium<ref>{{Cite journal|last=Medford|first=Arielle J.|last2=Velimirovic|first2=Marko|last3=Gefen|first3=Yifat|last4=Niemierko|first4=Andrzej|last5=Gerratana|first5=Lorenzo|last6=Davis|first6=Andrew A.|last7=Clifton|first7=Katherine|last8=Keenan|first8=Jennifer|last9=Podany|first9=Emily|date=2025-08|title=Genomic and proteomic profiling of GATA3 mutant metastatic hormone receptor-positive breast cancer and impact on clinical outcomes|url=https://pubmed.ncbi.nlm.nih.gov/40439821|journal=Breast Cancer Research and Treatment|volume=212|issue=3|pages=437–447|doi=10.1007/s10549-025-07710-w|issn=1573-7217|pmc=12209021|pmid=40439821}}</ref>
|-
|ERBB2
|Activating mutations, amplification
|Oncogene
|Recurrent
|D, P, T
|Yes (NCCN)
|Drives HER2 signaling and may guide targeted therapy decisions.
|-
|MAP3K1
|Inactivating mutations
|TSG
|Recurrent
|P
|No
|Implicated in MAPK signaling and luminal breast cancer development.
|-
|CDH1
|Inactivating mutations
|TSG
|Rare
|P
|Yes
|Loss of E-cadherin disrupts cell adhesion and promotes tumor progression.
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|
|-
|
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|
|
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
==Epigenomic Alterations==
==Epigenomic Alterations==
Put your text here
Epigenetic changes in breast tumor development include alterations in DNA methylation and chromatin remodeling. Hyper-methylation of tumor suppressor gene promoters, such as RASSF1A, CDH1, and BRCA1, in breast tumor samples has been documented and is believed to lead to gene silencing. Abnormalities in histone modification and chromatin remodeling are also known to affect gene expression patterns controlling cell proliferation and differentiation.
 
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|PIK3CA, AKT1; activating mutations
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|PI3K-AKT-mTOR signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|Increased cell proliferation and survival
|-
|PTEN; inactivating mutations
|PI3K-AKT-mTOR signaling
|Increased cell proliferation and survival
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|TP53; inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|DNA damage response
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|Genomic instability and tumor progression
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|ERBB2; amplification or activating mutations
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|MAPK/PI3K signaling pathways
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|Enhanced growth signaling and tumorigenesis
|-
|-
|
|GATA3; inactivating mutations
|
|Estrogen signaling pathways
|
|Altered luminal epithelial cell differentiation
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
Genetic alterations in breast cancers can be identified through various molecular diagnostic methods. Next-generation sequencing (NGS) panel tests may be used to identify somatic mutations in PIK3CA, TP53, and GATA3 genes. Immunohistochemistry and in situ hybridization (ISH) are used to identify overexpression and amplification of the ERBB2 (HER2) gene, respectively. In addition, various PCR tests and comparative genomic hybridization (CGH) may be used to identify particular mutations and copy number variations.
 
==Familial Forms==
==Familial Forms==
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
While the majority of breast tumors are considered to be sporadic, some cases are linked with hereditary cancer syndromes. Germline mutations in BRCA1 and BRCA2, PALB2, and CHEK2 are the most common genes associated with a hereditary predisposition to breast cancer. Additional susceptibility genes include TP53, which causes Li-Fraumeni syndrome, and PTEN, which causes Cowden syndrome.
 
==Additional Information==
==Additional Information==
Put your text here
Breast tumors are a diverse group of neoplastic disorders that vary in their molecular and histopathologic characteristics. Recent advances in genomic profiling have significantly enhanced our current understanding of tumor biology and have paved the way to develop novel therapeutic strategies. Molecular classification and genetic testing are assuming a significant role in diagnosis, prognosis, and treatment of breast cancer.
 
==Links==
==Links==
Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
WHO Classification of Tumours – Breast Tumours: <nowiki>https://publications.iarc.fr/581</nowiki>
 
cBioPortal for Cancer Genomics: <nowiki>https://www.cbioportal.org/</nowiki>
 
COSMIC – Catalogue of Somatic Mutations in Cancer: <nowiki>https://cancer.sanger.ac.uk/cosmic</nowiki>
 
The Cancer Genome Atlas (TCGA) Breast Cancer Dataset: <nowiki>https://www.cancer.gov/tcga</nowiki>
 
==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
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