Frequency of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathway pathogenic alterations in EUS-FNA sampled malignant lymph nodes in rectal cancer with theranostic potential

Ferga C. Gleeson, Benjamin R. Kipp, Jesse S. Voss, Michael B. Campion, Douglas M. Minot, Zheng J. Tu, Eric W Klee, Rondell Graham, Konstantinos N Lazaridis, Michael R. Henry, Michael J. Levy

Research output: Contribution to journalArticle

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Abstract

Background Targeted next-generation sequencing has the potential to stratify a tumor by molecular subtype and aid the development of a biomarker profile for prognostic risk stratification and theranostic potential. Objective To assess the frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens. Design Multigene molecular profiling of archived malignant EUS-FNA lymph node cytology specimens using the Ion Ampliseq Cancer Hotspot Panel v2, which targets at least 2855 possible mutations within 50 cancer-associated genes. Setting Single tertiary referral center. Patients Sporadic, treatment naive, locally advanced primary rectal cancer by EUS-FNA (n = 76) who subsequently completed neoadjuvant therapy with on-site oncologic surgery. Main Outcome Measurements The frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens by the mitogen-activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling pathways, by KRAS or NRAS wild-type lymph node status, by extramesenteric lymph node status, and by a complete pathologic response status. Results Eleven patients (14.5%) were 50-gene panel wild-type. Sixty-five patients had 139 pathogenic alterations (2 [1-3] per patient) in 13 of 50 evaluated genes. The following represent a spectrum of identified alterations: TP53 (n = 52; 68.4%), APC (n = 36; 47.4%), KRAS (n = 22; 28.9%), FBXW7 (n = 8; 10.5%), NRAS (n = 6; 7.9%), PIK3CA (n = 4; 5.3%), SMAD4 (n = 3; 3.9%), and BRAF (n = 3; 3.9%). Pathogenic alterations were identified in the MAPK and PI3K signaling pathways in 41% and 5% of patients, respectively. Limitations Findings were limited to a 50 cancer-associated gene analysis. Conclusions Molecular EUS lymph node assessments using cancer "hotspot" panels can identify pathogenic alteration frequency and distribution and have theranostic potential for individualized patient care.

Original languageEnglish (US)
Pages (from-to)550-556
Number of pages7
JournalGastrointestinal Endoscopy
Volume82
Issue number3
DOIs
StatePublished - Sep 1 2015

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MAP Kinase Kinase 3
Endoscopic Ultrasound-Guided Fine Needle Aspiration
1-Phosphatidylinositol 4-Kinase
Rectal Neoplasms
Lymph Nodes
Cell Biology
Neoplasm Genes
Neoplasms
Neoadjuvant Therapy
Mitogen-Activated Protein Kinases
Tertiary Care Centers
Genes
Theranostic Nanomedicine
Patient Care
Biomarkers
Ions
Mutation

ASJC Scopus subject areas

  • Gastroenterology
  • Radiology Nuclear Medicine and imaging

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Frequency of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathway pathogenic alterations in EUS-FNA sampled malignant lymph nodes in rectal cancer with theranostic potential. / Gleeson, Ferga C.; Kipp, Benjamin R.; Voss, Jesse S.; Campion, Michael B.; Minot, Douglas M.; Tu, Zheng J.; Klee, Eric W; Graham, Rondell; Lazaridis, Konstantinos N; Henry, Michael R.; Levy, Michael J.

In: Gastrointestinal Endoscopy, Vol. 82, No. 3, 01.09.2015, p. 550-556.

Research output: Contribution to journalArticle

Gleeson, Ferga C. ; Kipp, Benjamin R. ; Voss, Jesse S. ; Campion, Michael B. ; Minot, Douglas M. ; Tu, Zheng J. ; Klee, Eric W ; Graham, Rondell ; Lazaridis, Konstantinos N ; Henry, Michael R. ; Levy, Michael J. / Frequency of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathway pathogenic alterations in EUS-FNA sampled malignant lymph nodes in rectal cancer with theranostic potential. In: Gastrointestinal Endoscopy. 2015 ; Vol. 82, No. 3. pp. 550-556.
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abstract = "Background Targeted next-generation sequencing has the potential to stratify a tumor by molecular subtype and aid the development of a biomarker profile for prognostic risk stratification and theranostic potential. Objective To assess the frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens. Design Multigene molecular profiling of archived malignant EUS-FNA lymph node cytology specimens using the Ion Ampliseq Cancer Hotspot Panel v2, which targets at least 2855 possible mutations within 50 cancer-associated genes. Setting Single tertiary referral center. Patients Sporadic, treatment naive, locally advanced primary rectal cancer by EUS-FNA (n = 76) who subsequently completed neoadjuvant therapy with on-site oncologic surgery. Main Outcome Measurements The frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens by the mitogen-activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling pathways, by KRAS or NRAS wild-type lymph node status, by extramesenteric lymph node status, and by a complete pathologic response status. Results Eleven patients (14.5{\%}) were 50-gene panel wild-type. Sixty-five patients had 139 pathogenic alterations (2 [1-3] per patient) in 13 of 50 evaluated genes. The following represent a spectrum of identified alterations: TP53 (n = 52; 68.4{\%}), APC (n = 36; 47.4{\%}), KRAS (n = 22; 28.9{\%}), FBXW7 (n = 8; 10.5{\%}), NRAS (n = 6; 7.9{\%}), PIK3CA (n = 4; 5.3{\%}), SMAD4 (n = 3; 3.9{\%}), and BRAF (n = 3; 3.9{\%}). Pathogenic alterations were identified in the MAPK and PI3K signaling pathways in 41{\%} and 5{\%} of patients, respectively. Limitations Findings were limited to a 50 cancer-associated gene analysis. Conclusions Molecular EUS lymph node assessments using cancer {"}hotspot{"} panels can identify pathogenic alteration frequency and distribution and have theranostic potential for individualized patient care.",
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T1 - Frequency of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathway pathogenic alterations in EUS-FNA sampled malignant lymph nodes in rectal cancer with theranostic potential

AU - Gleeson, Ferga C.

AU - Kipp, Benjamin R.

AU - Voss, Jesse S.

AU - Campion, Michael B.

AU - Minot, Douglas M.

AU - Tu, Zheng J.

AU - Klee, Eric W

AU - Graham, Rondell

AU - Lazaridis, Konstantinos N

AU - Henry, Michael R.

AU - Levy, Michael J.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Background Targeted next-generation sequencing has the potential to stratify a tumor by molecular subtype and aid the development of a biomarker profile for prognostic risk stratification and theranostic potential. Objective To assess the frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens. Design Multigene molecular profiling of archived malignant EUS-FNA lymph node cytology specimens using the Ion Ampliseq Cancer Hotspot Panel v2, which targets at least 2855 possible mutations within 50 cancer-associated genes. Setting Single tertiary referral center. Patients Sporadic, treatment naive, locally advanced primary rectal cancer by EUS-FNA (n = 76) who subsequently completed neoadjuvant therapy with on-site oncologic surgery. Main Outcome Measurements The frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens by the mitogen-activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling pathways, by KRAS or NRAS wild-type lymph node status, by extramesenteric lymph node status, and by a complete pathologic response status. Results Eleven patients (14.5%) were 50-gene panel wild-type. Sixty-five patients had 139 pathogenic alterations (2 [1-3] per patient) in 13 of 50 evaluated genes. The following represent a spectrum of identified alterations: TP53 (n = 52; 68.4%), APC (n = 36; 47.4%), KRAS (n = 22; 28.9%), FBXW7 (n = 8; 10.5%), NRAS (n = 6; 7.9%), PIK3CA (n = 4; 5.3%), SMAD4 (n = 3; 3.9%), and BRAF (n = 3; 3.9%). Pathogenic alterations were identified in the MAPK and PI3K signaling pathways in 41% and 5% of patients, respectively. Limitations Findings were limited to a 50 cancer-associated gene analysis. Conclusions Molecular EUS lymph node assessments using cancer "hotspot" panels can identify pathogenic alteration frequency and distribution and have theranostic potential for individualized patient care.

AB - Background Targeted next-generation sequencing has the potential to stratify a tumor by molecular subtype and aid the development of a biomarker profile for prognostic risk stratification and theranostic potential. Objective To assess the frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens. Design Multigene molecular profiling of archived malignant EUS-FNA lymph node cytology specimens using the Ion Ampliseq Cancer Hotspot Panel v2, which targets at least 2855 possible mutations within 50 cancer-associated genes. Setting Single tertiary referral center. Patients Sporadic, treatment naive, locally advanced primary rectal cancer by EUS-FNA (n = 76) who subsequently completed neoadjuvant therapy with on-site oncologic surgery. Main Outcome Measurements The frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens by the mitogen-activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling pathways, by KRAS or NRAS wild-type lymph node status, by extramesenteric lymph node status, and by a complete pathologic response status. Results Eleven patients (14.5%) were 50-gene panel wild-type. Sixty-five patients had 139 pathogenic alterations (2 [1-3] per patient) in 13 of 50 evaluated genes. The following represent a spectrum of identified alterations: TP53 (n = 52; 68.4%), APC (n = 36; 47.4%), KRAS (n = 22; 28.9%), FBXW7 (n = 8; 10.5%), NRAS (n = 6; 7.9%), PIK3CA (n = 4; 5.3%), SMAD4 (n = 3; 3.9%), and BRAF (n = 3; 3.9%). Pathogenic alterations were identified in the MAPK and PI3K signaling pathways in 41% and 5% of patients, respectively. Limitations Findings were limited to a 50 cancer-associated gene analysis. Conclusions Molecular EUS lymph node assessments using cancer "hotspot" panels can identify pathogenic alteration frequency and distribution and have theranostic potential for individualized patient care.

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